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Find video protocols related to scientific articles indexed in Pubmed.
Comparison of Magnetic Intensities for Mesenchymal Stem Cell Targeting Therapy on Ischemic Myocardial Repair: High Magnetic Intensity Improves Cell Retention but Has No Additional Functional Benefit.
Cell Transplant
PUBLISHED: 11-07-2014
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Magnetic targeting has the potential to enhance the therapeutic effects of stem cells through increasing retention of transplanted cells. To investigate the effects of magnetic targeting intensities on cell transplantation, we performed different magnetic intensities for mesenchymal stem cells (MSCs) targeting-therapy in a rat model of ischemia/reperfusion.
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Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53 pathway in mice.
J Am Heart Assoc
PUBLISHED: 09-20-2014
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Increasing evidence suggests a critical role for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in protection against cardiac injuries; however, the downstream cytosolic actions of this enzyme are largely undefined.
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Influence of soil mercury concentration and fraction on bioaccumulation process of inorganic mercury and methylmercury in rice (Oryza sativa L.).
Environ Sci Pollut Res Int
PUBLISHED: 09-02-2014
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Recent studies showed that rice is the major pathway for methylmercury (MeHg) exposure to inhabitants in mercury (Hg) mining areas in China. There is, therefore, a concern regarding accumulation of Hg in rice grown in soils with high Hg concentrations. A soil pot experimental study was conducted to investigate the effects of Hg-contaminated soil on the growth of rice and uptake and speciation of Hg in the rice. Our results imply that the growth of rice promotes residual fraction of Hg transforming to organic-bound fraction in soil and increased the potential risks of MeHg production. Bioaccumulation factors deceased for IHg but relatively stabilized for MeHg with soil total mercury (THg) increasing. IHg in soil was the major source of Hg in the root and stalk, but leaf was contributed by Hg from both atmosphere and soil. Soluble and exchangeable Hg fraction can predict the bioavailability of IHg and MeHg in soils, and that can provide quantitative description of the rate of uptake of the bioavailable Hg. Soluble and exchangeable Hg fraction in paddy soil exceeding 0.0087 mg kg(-1) may cause THg concentration in rice grain above the permissible limit standard, and MeHg concentration in paddy soil more than 0.0091 mg kg(-1) may have the health risks to humans.
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miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation.
Sci China Life Sci
PUBLISHED: 08-29-2014
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microRNA-210 (miR-210) has generally been reported to be associated with cell survival under hypoxia. However, there are few data regarding the role of miR-210 in the survival of mesenchymal stem cells (MSCs) under oxidative stress conditions. Thus, we sought to investigate whether miR-210 over-expression could protect MSCs against oxidative stress injury and what the primary mechanisms involved are. The results showed that over-expression of miR-210 significantly reduced the apoptosis of MSCs under oxidative stress, accompanied by obvious increases in cell viability and superoxide dismutase activity and remarkable decreases in malonaldehyde content and reactive oxygen species production, resulting in a noticeable reduction of apoptotic indices when compared with the control. Moreover, the above beneficial effects of miR-210 could be significantly reduced by c-Met pathway repression. Collectively, these results showed that miR-210 over-expression improved MSC survival under oxidative stress through antioxidation and c-Met pathway activation, indicating the potential development of a novel approach to enhance the efficacy of MSC-based therapy for injured myocardium.
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A pilot study of angiogenin in heart failure with preserved ejection fraction: a novel potential biomarker for diagnosis and prognosis?
J. Cell. Mol. Med.
PUBLISHED: 08-15-2014
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Characteristics of heart failure with preserved ejection fraction (HFPEF) have not yet been fully understood. The objectives of this pilot study are to detect protein expression profile in the sera of HFPEF patients, and to identify potential biomarkers for the disease. Five hundred and seven proteins were detected in the sera of healthy volunteers and patients with either HFPEF or hypertension using antibody microarrays (three in each group). The results showed that the serum concentrations of 17 proteins (e.g. angiogenin, activin A and artemin) differed considerably between HFPEF and non-HFPEF patients (hypertensive patients and healthy controls), while a protein expression pattern distinct from that in non-HFPEF patients was associated with HFPEF patients. The up-regulation of angiogenin in both HFPEF patients with LVEF ?50% (P = 0.004) and a subset of HFPEF patients with LVEF = 41-49% (P < 0.001) was further validated in 16 HFPEF patients and 16 healthy controls. Meanwhile, angiogenin distinguished HFPEF patients from controls with a mean area under the receiver operating characteristic curve of 0.88 (P < 0.001) and a diagnostic cut-off point of 426 ng/ml. Moreover, the angiogenin levels in HFPEF patients were positively correlated with Lg(N-terminal pro-B-type natriuretic peptide, NT-proBNP) (P < 0.001). In addition, high angiogenin level (?426 ng/ml) was a predictor of all-cause death within a short-term follow-up duration, but not in the longer term of 36 months. This pilot study indicates that the aforementioned 17 potential biomarkers, such as angiogenin, may hold great promise for both diagnosis and prognosis assessment of HFPEF.
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miRNA-130b is required for the ERK/FOXM1 pathway activation-mediated protective effects of isosorbide dinitrate against mesenchymal stem cell senescence induced by high glucose.
Int. J. Mol. Med.
PUBLISHED: 07-15-2014
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The present study was carried out to investigate the hypothesis that organic nitrates can attenuate the senescence of mesenchymal stem cells (MSCs), a superior cell source involved in the regeneration and repair of damaged tissue. MSCs were treated with high glucose (HG) in order to induce senescence, which was markedly attenuated by pre-treatment with isosorbide dinitrate (ISDN), a commonly used nitrate, as indicated by senescence-associated galactosidase (SA-?-gal) activity, p21 expression, as well as by the mRNA levels of DNA methyltransferase 1 (DNMT1) and differentiated embryo chondrocyte expressed gene 1 (DEC1), which are senescence-related biomarkers. It was also found that the senescent MSCs (induced by HG glucose) exhibited a marked downregulation in ERK activity and forkhead box M1 (FOXM1) expression, which was reversed by ISDN preconditioning. Of note, the inhibition of ERK phosphorylation or the downregulation of FOXM1 statistically abolished the favourable effects of ISDN. In addition, the investigation of the senescence-associated miR-130 family suggested that miR-130b mediates the beneficial effects of ISDN; it was found that the protective effects of ISDN against the senescence of MSCs were prominently reversed by the knockdown of miR-130b. Furthermore, the downregulation of ERK phosphorylation or FOXM1 expression decreased the miR-130b expression level; however, the suppression of miR-130b demonstrated no significant impact on ERK phosphorylation or FOXM1 expression. Taken together, to the best of our knowledge, the present study is the first to demonstrate the favourable effects of ISDN against HG-induced MSC senescence, which are mediated through the activation of the ERK/FOXM1 pathway and the upregulation of miR-130b.
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Atorvastatin represses the angiotensin 2-induced oxidative stress and inflammatory response in dendritic cells via the PI3K/Akt/Nrf 2 pathway.
Oxid Med Cell Longev
PUBLISHED: 07-03-2014
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Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play a complex role in both the initiation and progression of atherosclerosis. We tested the hypothesis that the anti-inflammatory and antioxidant effects of atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein kinase B/transcription factor nuclear factor-erythroid 2-related factor 2 (PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the inflammatory and oxidative stress responses. This study showed that angiotensin 2 (Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86 expression, and increased the secretion of IL-12p70, IL-6, and TNF-?. These effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2 via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a process that was reversed by the PI3K inhibitor LY294002. Therefore, the regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in the regulation of the statin-mediated antioxidant and anti-inflammatory responses in DCs.
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Nine-month angiographic and two-year clinical follow-up of polymer-free sirolimus-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease: the Nano randomized trial.
Chin. Med. J.
PUBLISHED: 06-04-2014
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First generation drug-eluting stents (DES) were associated with a high incidence of late stent thrombosis (ST), mainly due to delayed healing and re-endothelization by the durable polymer coating. This study sought to assess the safety and efficacy of the Nano polymer-free sirolimus-eluting stent (SES) in the treatment of patients with de novo coronary artery lesions.
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Isosorbide dinitrate inhibits mechanical stress-induced cardiac hypertrophy and autophagy through downregulation of angiotensin II type 1 receptor.
J. Cardiovasc. Pharmacol.
PUBLISHED: 06-03-2014
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Mechanical stress can induce cardiac hypertrophy and autophagy. Recently, it has been reported that NO donors inhibited autophagy in human chondrocytes. Therefore, the effect of isosorbide dinitrate (ISDN) on cardiac hypertrophy and autophagy induced by mechanical stress was investigated in the present study. A 48-hour mechanical stretch and a 4-week transverse aortic constriction (TAC) were performed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, prior to the assessment of myocardial autophagy using LC3b-II. ISDN was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Furthermore, mechanical stress was shown to upregulate angiotensin II (AngII) type1 (AT1) receptor expression in both cultured cardiomyocytes and in mouse hearts, while ISDN was demonstrated to significantly suppress the upregulation of the AT1 receptor. It was concluded that ISDN could inhibit mechanical stress-induced cardiac hypertrophy and autophagy through the downregulation of AT1 receptor expression.
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A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial cells via modulating PPAR?-dependent AMPK/eNOS pathway.
J. Cell. Mol. Med.
PUBLISHED: 05-23-2014
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Thiazolidinediones, the antidiabetic agents such as ciglitazone, has been proved to be effective in limiting atherosclerotic events. However, the underlying mechanism remains elucidative. Ox-LDL receptor-1 (LOX-1) plays a central role in ox-LDL-mediated atherosclerosis via endothelial nitric oxide synthase (eNOS) uncoupling and nitric oxide reduction. Therefore, we tested the hypothesis that ciglitazone, the PPAR? agonist, protected endothelial cells against ox-LDL through regulating eNOS activity and LOX-1 signalling. In the present study, rat microvascular endothelial cells (RMVECs) were stimulated by ox-LDL. The impact of ciglitazone on cell apoptosis and angiogenesis, eNOS expression and phosphorylation, nitric oxide synthesis and related AMPK, Akt and VEGF signalling pathway were observed. Our data showed that both eNOS and Akt phosphorylation, VEGF expression and nitric oxide production were significantly decreased, RMVECs ageing and apoptosis increased after ox-LDL induction for 24 hrs, all of which were effectively reversed by ciglitazone pre-treatment. Meanwhile, phosphorylation of AMP-activated protein kinase (AMPK) was suppressed by ox-LDL, which was also prevented by ciglitazone. Of interest, AMPK inhibition abolished ciglitazone-mediated eNOS function, nitric oxide synthesis and angiogenesis, and increased RMVECs ageing and apoptosis. Further experiments showed that inhibition of PPAR? significantly suppressed AMPK phosphorylation, eNOS expression and nitric oxide production. Ciglitazone-mediated angiogenesis and reduced cell ageing and apoptosis were reversed. Furthermore, LOX-1 protein expression in RMVECs was suppressed by ciglitazone, but re-enhanced by blocking PPAR? or AMPK. Ox-LDL-induced suppression of eNOS and nitric oxide synthesis were largely prevented by silencing LOX-1. Collectively, these data demonstrate that ciglitazone-mediated PPAR? activation suppresses LOX-1 and moderates AMPK/eNOS pathway, which contributes to endothelial cell survival and function preservation.
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Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway.
Biochim. Biophys. Acta
PUBLISHED: 05-01-2014
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Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2-/- mice in HE-stained myocardial tissue samples at 8weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2-/- TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
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Telocytes in mice bone marrow: electron microscope evidence.
J. Cell. Mol. Med.
PUBLISHED: 04-16-2014
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Telocytes (TCs) are a novel type of interstitial cell of whom presence has been recently documented in many tissues and organs. However, whether TCs exists in bone marrow is still not reported. This study aims to find out TCs in mice bone marrow by using scanning electron microscope (SEM) and transmission electron microscope (TEM). SEM images showed that in mice bone marrow most of TCs have small spherical cell body (usually 4-6 ?m diameter) with thin long telopodes (Tps; usually one to three). The longest Tp observed was about 70 ?m, with an uneven calibre. Direct intercellular contacts exist between TCs. TEM shows mitochondria within dilations of Tps. Also, by TEM, we show the close spatial relations of Tps with blood vessels. In conclusion, this study provides ultrastructural evidence regarding the existence of TCs in mice bone marrow, in situ.
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Scanning electron microscope evidence of telocytes in vasculature.
J. Cell. Mol. Med.
PUBLISHED: 04-16-2014
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Here, we here present scanning electron microscope data for the existent telocytes (TCs) on the endothelial surface of the wall of pig coronary arteries, internal thoracic arteries and carotid arteries. These cells have a small (8.39 ± 1.97 ?m/4.95 ± 0.91 ?m) cell body of different shapes (from round to triangular, depending on the number of cellular prolongations) with very long (of about 30 ?m) and thin cellular processes called telopodes (Tps), which have uneven calibre. The number of Tps ranges between 2 and 6. Tps typically present the alternation of podoms and podomers, and also have a dichotomic branching pattern. These data could influence the current attempts for elucidating the role(s) of TCs.
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Hydrogen sulfide attenuates the recruitment of CD11b?Gr-1? myeloid cells and regulates Bax/Bcl-2 signaling in myocardial ischemia injury.
Sci Rep
PUBLISHED: 04-04-2014
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Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b(+)Gr-1(+) myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b(+)Gr-1(+) myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b(+)Gr-1(+) myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling.
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The frequency of invariant natural killer T cells correlates with the severity of myocarditis.
Viral Immunol.
PUBLISHED: 04-04-2014
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Invariant natural killer T cells (iNKT) perform different functions in different diseases. The cells were reported to protect myocarditis. However, the detail relationships between iNKT and Coxsackievirus B3 (CVB3)-induced myocarditis remain unclear. In order to investigate the correlation between the severity of CVB3-induced inflammation infiltration and the proportion of iNKT in the spleen and circulating blood, BALB/c mice were grouped into three groups according to the inflammation infiltration area of heart sections. The proportion of iNKT in CD3-positive cells in the spleen correlated negatively with the inflammation area (linear fit; R(2)=0.93) and virus capsid protein VP1 (linear fit; R(2)=0.84) in the myocardial tissue, while the proportion of iNKT in CD3-positive cells in the PBMC positively correlated with the inflammation area (linear fit; R(2)=0.91) and virus capsid protein VP1 (linear fit; R(2)=0.93) in the myocardial tissue. The results imply that iNKT might be used as a parameter for the diagnosis of myocarditis in clinical practice.
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Early clinical experience with a novel self-expanding percutaneous stent-valve in the native right ventricular outflow tract.
Catheter Cardiovasc Interv
PUBLISHED: 03-31-2014
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Balloon expandable transcatheter pulmonary valve systems are not applicable to the large majority of patients with chronic severe pulmonary regurgitation (PR) following surgical right ventricular outflow tract (RVOT) rehabilitation. This report describes the clinical use and short-term follow-up of a novel transcatheter self-expanding pulmonary valve system (Venus P Valve) for rehabilitation of the RVOT in patients with chronic severe PR.
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Rationale for and design of the Acarbose Cardiovascular Evaluation (ACE) trial.
Am. Heart J.
PUBLISHED: 03-17-2014
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Patients with cardiovascular disease and impaired glucose tolerance are at increased risk of cardiovascular events and type 2 diabetes mellitus (T2DM). Lifestyle modification or pharmacological intervention can delay progression to T2DM, but there is no clear evidence that they reduce cardiovascular risk in this population. Acarbose, an ?-glucosidase inhibitor that lowers postprandial blood glucose, has been shown to reduce T2DM risk by 25%, and possibly cardiovascular risk in impaired glucose tolerance subjects without cardiovascular disease.
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Mitochondrial aldehyde dehydrogenase 2 accentuates aging-induced cardiac remodeling and contractile dysfunction: role of AMPK, Sirt1, and mitochondrial function.
Free Radic. Biol. Med.
PUBLISHED: 03-14-2014
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Cardiac aging is associated with compromised myocardial function and morphology although the underlying mechanism remains elusive. Aldehyde dehydrogenase 2 (ALDH2), an essential mitochondrial enzyme governing cardiac function, displays polymorphism in humans. This study was designed to examine the role of ALDH2 in aging-induced myocardial anomalies. Myocardial mechanical and intracellular Ca(2+) properties were examined in young (4-5 months) and old (26-28 months) wild-type and ALDH2 transgenic mice. Cardiac histology, mitochondrial integrity, O2(-) generation, apoptosis, and signaling cascades, including AMPK activation and Sirt1 level were evaluated. Myocardial function and intracellular Ca(2+) handling were compromised with advanced aging; the effects were accentuated by ALDH2. Hematoxylin and eosin and Masson trichrome staining revealed cardiac hypertrophy and interstitial fibrosis associated with greater left-ventricular mass and wall thickness in aged mice. ALDH2 accentuated aging-induced cardiac hypertrophy but not fibrosis. Aging promoted O2(-) release, apoptosis, and mitochondrial injury (mitochondrial membrane potential, levels of UCP-2 and PGC-1?), and the effects were also exacerbated by ALDH2. Aging dampened AMPK phosphorylation and Sirt1, the effects of which were exaggerated by ALDH2. Treatment with the ALDH2 activator Alda-1 accentuated aging-induced O2(-) generation and mechanical dysfunction in cardiomyocytes, the effects of which were mitigated by cotreatment with activators of AMPK and Sirt1, AICAR, resveratrol, and SRT1720. Examination of human longevity revealed a positive correlation between life span and ALDH2 gene mutation. Taken together, our data revealed that ALDH2 enzyme may accentuate myocardial remodeling and contractile dysfunction in aging, possibly through AMPK/Sirt1-mediated mitochondrial injury.
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Hospital quality improvement initiative for patients with acute coronary syndromes in China: a cluster randomized, controlled trial.
Circ Cardiovasc Qual Outcomes
PUBLISHED: 03-11-2014
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Background- Substantial evidence-practice gaps exist in the management of acute coronary syndromes (ACS) in China. Clinical pathways are tools for improving ACS quality of care but have not been rigorously evaluated. Methods and Results- Between October 2007 and August 2010, a quality improvement program was conducted in 75 hospitals throughout China with mixed methods evaluation in a cluster randomized, controlled trial. Eligible hospitals were level 2 or level 3 centers routinely admitting >100 patients with ACS per year. Hospitals were assigned immediate implementation of the American Heart Association/American College of Cardiology guideline based clinical pathways or commencement of the intervention 12 months later. Outcomes were several key performance indicators reflecting the management of ACS. The key performance indicators were measured 12 months after commencement in intervention hospitals and compared with baseline data in control hospitals, using data collected from 50 consecutive patients in each hospital. Pathway implementation was associated with an increased proportion of patients discharged on appropriate medical therapy, with nonsignificant improvements or absence of effects on other key performance indicators. Conclusions- Among hospitals in China, the use of a clinical pathway for the treatment of ACS compared with usual care improved secondary prevention treatments, but effectiveness was otherwise limited. An accompanying process evaluation identified several health system barriers to more successful implementation. Clinical Trial Registration- URL: http://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.
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Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.
J. Cardiovasc. Pharmacol.
PUBLISHED: 03-08-2014
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To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway.
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Insulin-like growth factor binding protein 4 enhances cardiomyocytes induction in murine-induced pluripotent stem cells.
J. Cell. Biochem.
PUBLISHED: 03-05-2014
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Insulin-like growth factor binding protein 4 (IGFBP4) has been reported to play critical role in cardiomyocytes differentiation of embryonic stem cells (ESCs). But whether it promotes cardiomyocytes induction of iPSCs is unclear. In the present study, we aim to explore the role of IGFBP4 in the cardiogenesis of mouse iPSCs. We observed that IGFBP4 treatment at late stage during differentiation process of mouse iPSCs greatly enhanced the beating frequency of embryoid bodies (EBs). The expressions of Nkx2.5 (cardiac-specific transcription factor), ?-MHC, ?-actinin, and Troponin I (cardiac-specific protein) were significantly enhanced by IGFBP4 treatment. Immunostaining analysis showed that ?-MHC, TNNT2 and connexin 43, typical cardiac markers, were obviously expressed in isolated cardiomyocytes from iPSCs with or without IGFBP4 treatment. Further study revealed that IGFBP4 had little effect on the apoptosis of EBs, but it significantly promoted the proliferation of cardiomyocytes from iPSCs characterized by higher ratio EdU positive cells in differentiated cardiomyocytes. We next observed that IGFBP4 inhibited ?-catenin expression in cytosol of EBs at late stage during differentiation of iPSCs. Knockdown of ?-catenin using a siRNA technique promoted the proliferation of differentiated cardiomyocytes and enhanced cardiomyocytes induction of iPSCs, suggesting that the effect of IGFBP4 on cardiomyocytes differentiation of iPSCs has relationship with ?-catenin signaling pathway. In conclusion, IGFBP4 promotes cardiogenesis of iPSCs by enhancing the proliferation of differentiated cardiomyocytes through inhibiting ?-catenin signaling.
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Delivery of alginate-chitosan hydrogel promotes endogenous repair and preserves cardiac function in rats with myocardial infarction.
J Biomed Mater Res A
PUBLISHED: 03-03-2014
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The regenerative potential of alginate-chitosan composite in bone and cartilage tissue has been well documented, but its potential utility in cardiac tissue engineering has remained unknown. This study sought to determine whether early intramyocardial injection of alginate-chitosan could prevent left ventricular (LV) remodeling after myocardial infarction (MI), leading to a more favorable course of tissue restoration. In a rat model of acute MI, local injection of alginate-chitosan hydrogel into the peri-infarct zone preserved scar thickness, attenuated infarct expansion, and reduced scar fibrosis after 8 weeks, concomitantly with promoting increased angiogenesis and greater recruitment of endogenous repair at the infarct zone. Furthermore, this treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry. The cardiac function of the control-injected animals deteriorated over the 8-week course, while that of the hydrogel-injected animals did not.In addition, the hydrogel did not exacerbate inflammation in the heart. Intramyocardial injection of alginate-chitosan hydrogel represents a useful strategy to treat MI. It demonstrated marked therapeutic efficacies on various tissue levels after extensive MI, as well as potential to induce endogenous cardiomyocyte proliferation and recruit cardiac stem cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
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A prospective, multicenter, randomized trial of paclitaxel-coated balloon versus paclitaxel-eluting stent for the treatment of drug-eluting stent in-stent restenosis: results from the PEPCAD China ISR trial.
JACC Cardiovasc Interv
PUBLISHED: 02-22-2014
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The intention of the PEPCAD China ISR (A Prospective, Multicenter, Randomized Trial of Paclitaxel-Coated versus Paclitaxel-Eluting Stent for the Treatment of Drug-Eluting Stent In-Stent Restenosis) was to demonstrate the efficacy of paclitaxel-coated balloon (PCB) angioplasty in a non-European patient population with coronary drug-eluting stent in-stent restenosis (DES-ISR).
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Aldehyde dehydrogenase-2 is a host factor required for effective bone marrow mesenchymal stem cell therapy.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 02-20-2014
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Mesenchymal stem cell (MSC) therapy is a promising treatment for ischemic injury. However, the environmental regulatory mechanism is essentially unclear and thus greatly limits its application in clinical setting. Accumulating evidence suggests a vital role of aldehyde dehydrogenase-2 (ALDH2) in microenvironment homeostasis after ischemia. About 540 million people or 8% of population worldwide carry a loss-of-function allele of ALDH2. It is unknown whether ALDH2 functions as a host factor regulating the therapeutic potential of donor MSCs. Therefore, this study was designed to determine whether and how host ALDH2 regulates MSC retention and therapeutic efficacy after transplantation into ischemic tissues.
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Inducible metabolic adaptation promotes mesenchymal stem cell therapy for ischemia: a hypoxia-induced and glycogen-based energy prestorage strategy.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 02-20-2014
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Ischemic tissue is an environment with limited oxygen and nutrition availability. The poor retention of mesenchymal stem cells (MSC) in ischemic tissues greatly limits their therapeutic potential. The aim of this study was to determine whether and how inducible metabolic adaptation enhances MSC survival and therapy under ischemia.
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Limited value of recovery phase-limited ST segment depression of treadmill exercise test.
Chin. Med. J.
PUBLISHED: 02-19-2014
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Clinical meaning of recovery phase limited ST segment depression of a treadmill exercise test is controversial. The aim of this study was to re-assess the diagnostic and prognostic value of ST segment depression during the recovery phase with the active phase of a treadmill exercise test in suspected coronary artery disease patients.
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Elevated pulmonary artery pressure predicts poor outcome after cardiac resynchronization therapy.
J Interv Card Electrophysiol
PUBLISHED: 02-18-2014
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Pulmonary artery hypertension is correlated with poor clinical prognosis in patients with chronic heart failure. However, there is a paucity of data concerning the impact of baseline pulmonary artery systolic pressure (PASP) on clinical outcome after cardiac resynchronization therapy (CRT). The aim of the study is to evaluate the association of baseline PASP with CRT response.
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Streptococcus acidominimus causing invasive disease in humans: a case series.
J Med Case Rep
PUBLISHED: 02-17-2014
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Streptococcus acidominimus is a member of the viridans group streptococci and is rarely pathogenic in humans, making it difficult to assess its epidemiologic and clinical significance.
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Influence of cardioversion on asymptomatic cerebral lesions following atrial fibrillation ablation.
J Interv Card Electrophysiol
PUBLISHED: 02-13-2014
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Asymptomatic cerebral lesions detected by diffusion-weighted magnetic resonance imaging (MRI) following atrial fibrillation (AF) ablation were reported in recent years. It was reported that cardioversion during the procedure of AF ablation was one independent risk factor of asymptomatic cerebral lesions. However, in some studies, the similar association between asymptomatic cerebral lesions and intraprocedural cardioversion was not observed. Given the inconsistent results, we did a meta-analysis to explore the influence of intraprocedural cardioversion on the asymptomatic cerebral lesions detected by MRI following AF ablation.
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Knockdown of nucleosome assembly protein 1-like 1 induces mesoderm formation and cardiomyogenesis via notch signaling in murine-induced pluripotent stem cells.
Stem Cells
PUBLISHED: 02-11-2014
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Low efficiency of cardiomyocyte differentiation from induced pluripotent stem cells (iPSCs) hinders the clinical application of iPSC technology for cardiac repair strategy. Recently, we screened out nucleosome assembly protein 1-like 1 (Nap1l1), which was downregulated during the differentiation of P19CL6 cells into cardiomyocytes. Here, we attempted to study the role of Nap1l1 in cardiomyogenesis of iPSC. Nap1l1 was downregulated during the differentiation of iPSC. Knockdown of Nap1l1 dramatically enhanced the differentiation of iPSC into functional cardiomyocytes while overexpression of Nap1l1 sharply lowered the differentiation. Moreover, although Nap1l1-knockdown had little effect on endoderm differentiation, the Nap1l1 modulation significantly accelerated mesoderm development. Re-expressing Nap1l1 in Nap1l1-knockdown-iPSC rescued the effects of Nap1l1. Inducibly overexpressing Nap1l1 at early stage of differentiation greatly inhibited mesoderm induction and cardiogenesis of iPSC. However, mesoderm stem cells (Flk-1-positive cells) originated from Nap1l1-knockdown- or -overexpression-iPSC showed no difference in further cardiomyocyte differentiation compared with that of control-iPSC. Further study revealed that Nap1l1-overexpression increased ?-secretase activity and the expression of Notch intracellular domain (NICD) and downstream genes during the differentiation of iPSC. ?-Secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycinet-butyl ester) greatly suppressed the production of NICD and abolished the inhibitory effects of Nap1l1-overexpression on mesoderm induction and cardiogenesis. These findings demonstrate that downregulation of Nap1l1 significantly enhances mesodermal induction and subsequent cardiogenesis of murine iPSC via inhibition of ?-secretase-regulated Notch signaling, which would facilitate the application of iPSC in heart diseases.
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Aliskiren-attenuated myocardium apoptosis via regulation of autophagy and connexin-43 in aged spontaneously hypertensive rats.
J. Cell. Mol. Med.
PUBLISHED: 02-07-2014
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There are controversies about the mechanism of myocardium apoptosis in hypertensive heart disease. The aim of this study was to investigate the relationship among autophagy, Cx43 and apoptosis in aged spontaneously hypertensive rats (SHRs) and establish whether Aliskiren is effective or not for the treatment of myocardium apoptosis. Twenty-one SHRs aged 52 weeks were randomly divided into three groups, the first two receiving Aliskiren at a dose of 10 and 25 mg/kg/day respectively; the third, placebo for comparison with seven Wistar-Kyoto (WKY) as controls. After a 2-month treatment, systolic blood pressure (SBP), heart to bw ratios (HW/BW%) and angiotensin II (AngII) concentration were significantly enhanced in SHRs respectively. Apoptotic cardiomyocytes detected with TUNEL and immunofluorescent labelling for active caspase-3 increased nearly fourfolds in SHRs, with a decline in the expression of survivin and AKT activation, and an increase in caspase-3 activation and the ratio of Bax/Bcl-2. Myocardium autophagy, detected with immunofluorescent labelling for LC3-II, increased nearly threefolds in SHRs, with the up-regulation of Atg5, Atg16L1, Beclin-1 and LC3-II. The expression of Cx43 plaque was found to be down-regulated in SHRs. Aliskiren significantly reduced SBP, HW/BW%, AngII concentration and the expression of AT(1)R. Thus, Aliskiren protects myocardium against apoptosis by decreasing autophagy, up-regulating Cx43. These effects showed a dose-dependent tendency, but no significance. In conclusion, the myocardium apoptosis developed during the hypertensive end-stage of SHRs could be ameliorated by Aliskiren via the regulation of myocardium autophagy and maladaptive remodelling of Cx43.
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Myocardial transfection of hypoxia-inducible factor-1? and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction.
Stem Cell Res Ther
PUBLISHED: 02-05-2014
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Mesenchymal stem cells (MSCs) have potential for the treatment of myocardial infarction. However, several meta-analyses revealed that the outcome of stem cell transplantation is dissatisfactory. A series of studies demonstrated that the combination of cell and gene therapy was a promising strategy to enhance therapeutic efficiency. The aim of this research is to investigate whether and how the combination of overexpression of hypoxia-inducible factor-1? (HIF-1?) and co-transplantation of mesenchymal stem cells can enhance cardiac repair in myocardial infarction.
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Combination of CD34-positive cell subsets with infarcted myocardium-like matrix stiffness: a potential solution to cell-based cardiac repair.
J. Cell. Mol. Med.
PUBLISHED: 01-31-2014
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Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well-characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue-like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time-dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness-dependent differentiation of the unselected bone marrow-derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell-based cardiac repair. However, the difference in tissue stiffness-dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium-like matrix stiffness compared with CD34-negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell-based cardiac repair.
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Left ventricular remodeling with preserved function after coronary microembolization: the effect of methylprednisolone.
Eur. J. Med. Res.
PUBLISHED: 01-22-2014
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The objective of this study was to evaluate changes in left ventricular ejection fraction (LVEF) and left ventricular remodeling after coronary microembolization (CME) and to investigate the protective effects of methylprednisolone (MTP).
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Urotensin II inhibited the proliferation of cardiac side population cells in mice during pressure overload by JNK-LRP6 signalling.
J. Cell. Mol. Med.
PUBLISHED: 01-22-2014
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Cardiac side population cells (CSPs) are promising cell resource for the regeneration in diseased heart as intrinsic cardiac stem cells. However, the relative low ratio of CSPs in the heart limited the ability of CSPs to repair heart and improve cardiac function effectively under pathophysiological condition. Which factors limiting the proliferation of CSPs in diseased heart are unclear. Here, we show that urotensin II (UII) regulates the proliferation of CSPs by c-Jun N-terminal kinase (JNK) and low density lipoprotein receptor-related protein 6 (LRP6) signalling during pressure overload. Pressure overload greatly upregulated UII level in plasma, UII receptor (UT) antagonist, urantide, promoted CSPs proliferation and improved cardiac dysfunction during chronic pressure overload. In cultured CSPs subjected to mechanical stretch (MS), UII significantly inhibited the proliferation by UT. Nanofluidic proteomic immunoassay showed that it is the JNK activation, but not the extracellular signal-regulated kinase signalling, that involved in the UII-inhibited- proliferation of CSPs during pressure overload. Further analysis in vitro indicated UII-induced-phospho-JNK regulates phosphorylation of LRP6 in cultured CSPs after MS, which is important in the inhibitory effect of UII on the CSPs during pressure overload. In conclusion, UII inhibited the proliferation of CSPs by JNK/LRP6 signalling during pressure overload. Pharmacological inhibition of UII promotes CSPs proliferation in mice, offering a possible therapeutic approach for cardiac failure induced by pressure overload.
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Aldehyde dehydrogenase 2 ameliorates doxorubicin-induced myocardial dysfunction through detoxification of 4-HNE and suppression of autophagy.
J. Mol. Cell. Cardiol.
PUBLISHED: 01-03-2014
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Mitochondrial aldehyde dehydrogenase (ALDH2) protects against cardiac injury via reducing production of 4-hydroxynonenal (4-HNE) and ROS. This study was designed to examine the impact of ALDH2 on doxorubicin (DOX)-induced cardiomyopathy and mechanisms involved with a focus on autophagy. 4-HNE and autophagic markers were detected by Western blotting in ventricular tissues from normal donors and patients with idiopathic dilated cardiomyopathy. Cardiac function, 4-HNE and levels of autophagic markers were detected in WT, ALDH2 knockout or ALDH2 transfected mice treated with or without DOX. Autophagy regulatory signaling including PI-3K, AMPK and Akt was examined in DOX-treated cardiomyocytes incubated with or without ALDH2 activator Alda-1. DOX-induced myocardial dysfunction, upregulation of 4-HNE and autophagic proteins were further aggravated in ALDH2 knockout mice while they were ameliorated in ALDH2 transfected mice. DOX downregulated Class I and upregulated Class III PI3-kinase, the effect of which was augmented by ALDH2 deletion. Accumulation of 4-HNE and autophagic protein markers in DOX-induced cardiomyocytes was significantly reduced by Alda-1. DOX depressed phosphorylated Akt but not AMPK, the effect was augmented by ALDH2 knockout. The autophagy inhibitor 3-MA attenuated, whereas autophagy inducer rapamycin mimicked DOX-induced cardiomyocyte contractile defects. In addition, rapamycin effectively mitigated Alda-1-offered protective action against DOX-induced cardiomyocyte dysfunction. Our data further revealed downregulated ALDH2 and upregulated autophagy levels in the hearts from patients with dilated cardiomyopathy. Taken together, our findings suggest that inhibition of 4-HNE and autophagy may be a plausible mechanism underscoring ALDH2-offered protection against DOX-induced cardiac defect. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".
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Multimodal SPION-CREKA peptide based agents for molecular imaging of microthrombus in a rat myocardial ischemia-reperfusion model.
Biomaterials
PUBLISHED: 01-03-2014
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Microthrombosis plays a key role in many cardiovascular diseases. Although it is not difficult to localize thrombus within large or middle-sized vessels, the noninvasive diagnostic regimen for the detection of microthrombus remains scarce. Here we developed a nanoagent by conjucting superparamagnetic iron-oxide nanoparticle with fluorophore and a targeting element, CREKA, a peptide with special affinity for fibrin. In a rat model of myocardial ischemia-reperfusion (MI/R), the multimodal nanoagents were readily and selectively accumulated within microthrombosis, which was detectable by both magnetic resonance and optical imaging modalities. The fibrin-targeted nanoagent could be expected to have utility not only in molecular imaging of fibrin, understanding the mechanisms of microcirculation disorders, but also in targeted therapy with fibrinolytic agents.
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A comparison of the efficacy of surgical renal denervation and pharmacologic therapies in post-myocardial infarction heart failure.
PLoS ONE
PUBLISHED: 01-01-2014
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Although renal denervation (RD) has been shown to be effective in treating post- myocardial Infarction (MI) heart failure (HF) in animal models and clinical trials, its utility as a standalone treatment without traditional drug treatment for post-MI HF still needs to be investigated.
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Src is required for mechanical stretch-induced cardiomyocyte hypertrophy through angiotensin II type 1 receptor-dependent ?-arrestin2 pathways.
PLoS ONE
PUBLISHED: 01-01-2014
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Angiotensin II (AngII) type 1 receptor (AT1-R) can be activated by mechanical stress (MS) without the involvement of AngII during the development of cardiomyocyte hypertrophy, in which G protein-independent pathways are critically involved. Although ?-arrestin2-biased signaling has been speculated, little is known about how AT1-R/?-arrestin2 leads to ERK1/2 activation. Here, we present a novel mechanism by which Src kinase mediates AT1-R/?-arrestin2-dependent ERK1/2 phosphorylation in response to MS. Differing from stimulation by AngII, MS-triggered ERK1/2 phosphorylation is neither suppressed by overexpression of RGS4 (the negative regulator of the G-protein coupling signal) nor by inhibition of G?q downstream protein kinase C (PKC) with GF109203X. The release of inositol 1,4,5-triphosphate (IP3) is increased by AngII but not by MS. These results collectively suggest that MS-induced ERK1/2 activation through AT1-R might be independent of G-protein coupling. Moreover, either knockdown of ?-arrestin2 or overexpression of a dominant negative mutant of ?-arrestin2 prevents MS-induced activation of ERK1/2. We further identifies a relationship between Src, a non-receptor tyrosine kinase and ?-arrestin2 using analyses of co-immunoprecipitation and immunofluorescence after MS stimulation. Furthermore, MS-, but not AngII-induced ERK1/2 phosphorylation is attenuated by Src inhibition, which also significantly improves pressure overload-induced cardiac hypertrophy and dysfunction in mice lacking AngII. Finally, MS-induced Src activation and hypertrophic response are abolished by candesartan but not by valsartan whereas AngII-induced responses can be abrogated by both blockers. Our results suggest that Src plays a critical role in MS-induced cardiomyocyte hypertrophy through ?-arrestin2-associated angiotensin II type 1 receptor signaling.
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Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.
PLoS ONE
PUBLISHED: 01-01-2014
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Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC) were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT1 receptor blocker, but not PD123319, the AT2 inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.
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Association of renal biochemical parameters with left ventricular diastolic dysfunction in a community-based elderly population in China: a cross-sectional study.
PLoS ONE
PUBLISHED: 01-01-2014
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Relationship of left ventricular diastolic dysfunction (LVDD) with parameters that could provide more information than hemodynamic renal indexes has not been clarified. We aimed to explore the association of comprehensive renal parameters with LVDD in a community-based elderly population.
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Effect and mechanism of thrombospondin-1 on the angiogenesis potential in human endothelial progenitor cells: an in vitro study.
PLoS ONE
PUBLISHED: 01-01-2014
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Coronary collateral circulation plays a protective role in patients with coronary artery disease (CAD). We investigated whether thrombospondin-1(TSP-1) has an inhibitory effect on angiogenesis potential in endothelial progenitor cells(EPCs) and tested whether TSP-1 are altered in plasma of patients who had chronic total occlusion (CTO) in at least one coronary artery and with different collateral stages(according to Rentrop grading system).
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Managing hypercholesterolemia and preventing cardiovascular events in elderly and younger Chinese adults: focus on rosuvastatin.
Clin Interv Aging
PUBLISHED: 12-09-2013
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Coronary heart disease (CHD) is the leading cause of death worldwide. The efficacy and safety of statins in primary and secondary prevention of CHD is confirmed in several large studies, and rosuvastatin is the latest statin on market. We review the published literature on rosuvastatin in Chinese people. The pharmacokinetics of rosuvastatin in Chinese is somewhat different from that in Caucasians, but this does not influence the linear relationship between dosage and efficacy and with no drug accumulation. Rosuvastatin 5-20 mg/day is effective and safe in decreasing low-density lipoprotein cholesterol in both younger and elderly patients with hypercholesterolemia, even in very elderly patients. Rosuvastatin also shows anti-inflammatory and antiatherosclerosis features, such as reducing carotid intima-media thickness and plaque area. Rosuvastatin can also improve the prognosis of Chinese CHD patients, such as in the case of acute myocardial infarction. Its adverse-event rate is low and comparable to other statins. In conclusion, rosuvastatin is effective and safe for younger or elderly Chinese patients.
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Decline in platelet count after percutaneous transcatheter closure of congenital heart disease.
Acta Cardiol
PUBLISHED: 11-06-2013
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Decline in platelet count (DPC) in patients with congenital heart disease (CHD) undergoing percutaneous transcatheter closure (PTC) has seldom been reported. We sought to investigate the incidence, severity and predictors of DPC among patients with CHD undergoing PTC.
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Percutaneous device closure of ruptured sinus of valsalva aneurysm: a preliminary experience.
J Invasive Cardiol
PUBLISHED: 10-04-2013
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To evaluate the immediate and mid-term outcomes of percutaneous device closure using patent ductus arteriosus (PDA) or ventricular septal defect (VSD) occluders in patients with ruptured sinus of Valsalva aneurysm (RSVA).
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The effect of c-fos on acute myocardial infarction and the significance of metoprolol intervention in a rat model.
Cell Biochem. Biophys.
PUBLISHED: 08-28-2013
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Over-expression of c-fos may play a role in some diseases. Research pertaining to the expression of c-fos in acute myocardial ?nfarction (AMI) is rare, and the detailed role of c-fos in AMI has not been reported. Therefore, the purpose of this project was to elucidate the detailed effect of c-fos on AMI rats and evaluate the effect of a metoprolol intervention. An AMI rat model was established for the purposes of this study. The expression of c-fos in AMI was evaluated via immunohistochemical analysis and in situ hybridization. Simultaneously, we investigated the effect of c-fos on AMI rats via medicinal treatment with c-fos monoclonal antibody, isoproterenol, and metoprolol. Positive c-Fos protein expression and c-fos mRNA expression in cardiomyocytes were increased at 1, 3, 7, and 10 days after ligation in AMI rats compared with a sham-operated group. Peak expression occurred at 3 days after ligation. The weight percentage fraction of infarct size was decreased in rats treated with c-fos monoclonal antibody compared with the control normal saline treatment group. The weight percentage fraction of infarction size was increased after c-fos was increased via the administration of isoproterenol. c-Fos protein expression and the infarct size in rats treated with metoprolol were also decreased compared with the control normal saline treatment group. The results showed that c-fos expression rapidly increased after coronary ligation; c-fos plays an important role in myocardial lesions and is likely to be involved in the pathogenesis of AMI as well. Metoprolol can inhibit the expression of c-fos and has a positive therapeutic effect on rats after AMI; the involvement effect of metoprolol on myocardial infarction might be correlated with its effect on the inhibition of c-fos.
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Integration of cardiac proteome biology and medicine by a specialized knowledgebase.
Circ. Res.
PUBLISHED: 08-21-2013
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Omics sciences enable a systems-level perspective in characterizing cardiovascular biology. Integration of diverse proteomics data via a computational strategy will catalyze the assembly of contextualized knowledge, foster discoveries through multidisciplinary investigations, and minimize unnecessary redundancy in research efforts.
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Impact of interlead distance on immediate and mid-term response to cardiac resynchronization therapy.
Scand. Cardiovasc. J.
PUBLISHED: 08-14-2013
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It is currently recommended that the left ventricular (LV) lead be placed at the posterolateral or lateral wall of heart during cardiac resynchronization therapy (CRT). The aim of our study is to evaluate the influence of interlead distance on immediate and mid-term response to CRT with altered right ventricular (RV) pacing site.
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The effect of nonuniform magnetic targeting of intracoronary-delivering mesenchymal stem cells on coronary embolisation.
Biomaterials
PUBLISHED: 08-08-2013
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Magnetic targeting has been recently introduced to enhance cell retention in animals with acute myocardial infarction. However, it is unclear whether the magnetic accumulation of intravascular cells increases the risk of coronary embolism. Upon finite element analysis, we found that the permanent magnetic field was nonuniform, manifestated as attenuation along the vertical axis and polarisation along the horizontal axis. In the in vitro experiments, iron-labelled mesenchymal stem cells (MSCs) were accumulated in layers predominantly at the edge of the magnet. In an ischaemic rat model subjected to intracavitary MSCs injection, magnetic targeting induced unfavourable vascular embolisation and an inhomogeneous distribution of the donor cells, which prevented the enhanced cell retention from translating into additional functional benefit. These potential complications of magnetic targeting should be thoroughly investigated and overcome before clinical application.
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A new coronary retroinfusion technique in theRat infarct model: transjugular cardiac vein catheterization.
Exp. Anim.
PUBLISHED: 08-02-2013
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Cell delivery via the retrograde coronary route boasts less vessel embolism, myocardial injury, and arrhythmogenicity when compared with those via antegrade coronary administration or myocardial injection. However, conventional insertion into the coronary sinus and consequent bleeding complication prevent its application in small animals. To overcome the complication of bleeding, we described a modified coronary retroinfusion technique via the jugular vein route in rats with myocardial infarction (MI). A flexible wire with a bent end was inserted into the left internal jugular vein and advanced slowly along the left superior vena cava. Under direct vision, the wire was run into the left cardiac vein by rotating the wire and changing the position of its tip. A fine tube was then advanced along the wire to the left cardiac vein. This modified technique showed less lethal hemorrhage than the conventional technique. Retroinfusion via transjugular catheter enabled efficient fluid or cell dissemination to the majority areas of the free wall of the left ventricle, covering the infarcted anterior wall. In conclusion, transjugular cardiac vein catheterization may make retrocoronary infusion a more safe and practical route for delivering cell, drug, and gene therapy into the infarcted myocardium of rats.
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Coxsackievirus B3-induced calpain activation facilitates the progeny virus replication via a likely mechanism related with both autophagy enhancement and apoptosis inhibition in the early phase of infection: An in vitro study in H9c2 cells.
Virus Res.
PUBLISHED: 07-30-2013
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Calpain is a family of neutral cysteine proteinase involved in many physiological and pathological processes including virus replication, autophagy and apoptosis. Previous study has indicated the involvement of calpain in pathogenesis of coxsackievirus B3 (CVB3)-induced myocarditis. Besides, many studies demonstrated that host cell autophagy and apoptosis mechanisms participate in virus life cycle. However, role of calpain in CVB3 replication via autophagy/apoptosis mechanisms has not been reported, which was discussed here in H9c2 cardiomyocytes. The data demonstrated that calpain was activated following CVB3 infection. Calpain inhibition decreased autophagy, indicating role of calpain in enhancing autophagy during CVB3 infection. Both calpain activity and autophagy were involved in facilitating CVB3 replication demonstrated by virus titer and CVB3 capsid protein VP1 expression alterations resulting from calpain inhibitor ALLN and autophagy inhibitor 3MA intervention. We also found that both calpain activity and autophagy suppressed caspase3 activity and host cell apoptosis 5-10h post-infection (p.i.). In summary, the present study shows that CVB3 infection of H9c2 cells hinders caspase3 activity provocation and cell apoptosis at least in the early phase of infection (5-10h p.i.) via calpain-induced autophagy enhancement, which might be a mechanism facilitating CVB3 replication in host cells.
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Olmesartan attenuates cardiac remodeling through DLL4/Notch1 pathway activation in pressure overload mice.
J. Cardiovasc. Pharmacol.
PUBLISHED: 07-23-2013
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Notch1 signaling controls the cardiac adaptation to stress. We therefore aimed to validate whether olmesartan, a widely used angiotensin II type 1 receptor blocker, ameliorates cardiac remodeling and dysfunction via delta-like ligand 4 (DLL4)/Notch1 pathway in mice with chronic pressure overload.
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Solely abluminal drug release from coronary stents could possibly improve reendothelialization.
Catheter Cardiovasc Interv
PUBLISHED: 07-14-2013
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Objectives To compare a new stent with an asymmetric coating, eluting the drug to the abluminal surface, to a stent with a conventional coating eluting the drug both to the luminal and the abluminal side. Background Stents with asymmetric coating, eluting the drug to the vessel wall (BPSES-A), could potentially give faster reendothelialization after percutaneous coronary interventions (PCI) and decrease in in-stent thrombosis and late restenosis. Methods BPSES-A, conventional coated stents (BPSES-C), biodegradable polymer stents without drug (BPS, for control), and bare metal stents (BMS, for control) were implanted into the coronary arteries of 38 pigs (75 stents). Pigs were sacrificed after 4, 12 and 24 weeks. Quantitative coronary angiography (QCA) was used to compare in-stent late lumen loss (LLL) and electron microscopy was used to reveal levels of reendothelialization. Results The stents were all successfully implanted. LLL of BPSES-A, BPSES-C, BMS, and PBS were 0.56±0.51mm, 0.60±0.58mm, 0.89±0.43mm and 1.68±0.30mm respectively after 4 weeks. LLL of BPSES-A and BPSES-C were 0.63±0.53mm and 0.69±0.24mm respectively after 12 weeks. LLL of BPSES-A, BPSES-C and BMS were 0.42±0.15m, 0.56±0.28mm and 0.99±0.13mm respectively after 24 weeks. The scaling of reendothelialization was as follows: after 4 weeks BMS >= PBS > BPSES-A > BPSES-C, after 12 weeks BPSES-A > BPSES-C and after 24 weeks BMS > BPSES-A > BPSES-C. Reendothelialization was better in BPSES-A than BPSES-C (p < 0.05). There was no correlation between LLL and reendothelialization (p = 0.42). Conclusion Asymmetric coating of coronary stents might be helpful to improve reendothelialization. © 2013 Wiley Periodicals, Inc.
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A1180V of cardiac sodium channel gene (SCN5A): is it a risk factor for dilated cardiomyopathy or just a common variant in Han Chinese?
Dis. Markers
PUBLISHED: 06-17-2013
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Our previous study of a Chinese family with dilated cardiomyopathy (DCM) suggested that A1180V of the cardiac sodium channel gene (SCN5A) was associated with the disease within this family. According to data deposited in dbSNP, however, A1180V has been found in some small samples of the Asian population. In this study, we followed up the affected pedigree and expanded the investigation of the prevalence of A1180V in 460 unrelated healthy Han Chinese. Besides, we searched and analyzed it in other database as well. During the follow-up period, 1 A1180V carriers condition deteriorated a lot, and another 4 carriers progressed to DCM or atrioventricular block (AVB). We also found that the A1180V was absent among the 460 individuals (0%, 0/460), and the carrier frequency of A1180V among Chinese was about 0.51% obtained from the 1000 genome project. In conclusion, our finding suggests that A1180V is a potential risk factor for DCM, and it is extremely rare among Healthy Han Chinese.
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Exogenous taurine attenuates mitochondrial oxidative stress and endoplasmic reticulum stress in rat cardiomyocytes.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 04-27-2013
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Taurine, a conditionally essential amino acid, plays a critical role in cardiovascular function. Here we examined the effect of taurine on mitochondria and endoplasmic reticulum in rat cardiomyocytes during glucose deprivation (GD). Data showed that cell viability, intracellular taurine contents, and taurine transporter expression were decreased during GD. In contrast, an increase in reactive oxygen species and intracellular Ca(2+) contents was observed. GD also caused disrupted mitochondrial membrane potential, apoptotic cell death, and dissociation of unfolded protein response (UPR)-relative proteins in cardiomyocytes. Signal transduction analysis showed that Bcl-2 family protein balance was disturbed, caspase-12 was activated and UPR-relative protein levels were up-regulated. Moreover, pre-treatment with 80 mM exogenous taurine attenuated GD effect in cardiomyocytes. Our results suggest that taurine have beneficial effects on inhibiting mitochondria-dependent cell apoptosis and UPR-associated cell apoptosis and might have clinical implications on acute myocardial infarction in future.
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High glucose induces upregulation of scavenger receptors and promotes maturation of dendritic cells.
Cardiovasc Diabetol
PUBLISHED: 03-26-2013
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BACKGROUND: Both hyperglycaemia and dendritic cells (DCs) play causative roles in atherosclerosis. However, whether they interact in atherosclerosis remains uncertain. Therefore, we examined whether high glucose could regulate the expression of scavenger receptors responsible for oxidised low-density lipoprotein (oxLDL) uptake in DCs, a critical step in atherogenesis. In addition, we investigated the impact of glucose on DC maturation regarding changes in phenotype and cytokine secretion. METHODS: Immature DCs were cultured with different concentrations of glucose (5.5 mmol/L, 15 mmol/L, 30 mmol/L) in the absence or presence of N-acetylcysteine (NAC), SB203580 or Bay11-7082 for 24 hours. We used 30 mmol/L mannitol as a high-osmolarity control treatment. The expression of the scavenger receptors SR-A, CD36 and LOX-1 was determined by real-time PCR and western blot analysis. Furthermore, DCs were incubated with DiI-labelled oxLDL. The DiI-oxLDL-incorporated fraction was investigated by flow cytometry analysis. The intracellular production of ROS in DCs was measured by dichlorodihydrofluorescein (DCF) fluorescence using confocal microscopy. Finally, flow cytometry analysis was used to investigate immunophenotypic protein expression (CD83 and CD86). Supernatant cytokine measurements were used for immune function assays. RESULTS: The incubation of DCs with glucose enhanced, in a dose-dependent manner, the gene and protein expression of SR-A, CD36 and LOX-1. This effect was partially abolished by NAC, SB203580 and Bay11-7082. Incubation of DCs with mannitol (30 mmol/L) did not enhance these scavenger receptors expression. High glucose upregulated the production of ROS and expression of p38 MAPK in DCs. NAC partially reversed p38 MAPK upregulation. High glucose increased the oxLDL-uptake capacity of DCs. Blockage of the scavenger receptors SR-A and CD36 reduced oxLDL uptake, but blockage of LOX-1 did not. Furthermore, high-glucose (15 mmol/L or 30 mmol/L) treatment increased CD86 and CD83 in DCs. High glucose also increased IL-6 and IL-12 secretion and decreased IL-10 secretion. CONCLUSION: High glucose can increase the expression of the scavenger receptors SR-A, CD36 and LOX-1, which can increase the oxLDL-uptake capacity of DCs. High glucose induces a proinflammatory cytokine profile in human DCs, leading to DC maturation. These results support the hypothesis that atherosclerosis is aggravated by hyperglycaemia-induced DC activation and oxLDL uptake.
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Isolation, culture, and identification of amniotic fluid-derived mesenchymal stem cells.
Cell Biochem. Biophys.
PUBLISHED: 03-20-2013
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Amniotic fluid-derived mesenchymal stem cells (AF-MSC) are newly described, excellent seed cells that have good differentiation capability and are convenient to obtain. However, it is important to develop a method to isolate and culture AF-MSC efficiently. Amniotic fluid samples were obtained from rabbits and the adherence method was used for AF-MSC culture. Flow cytometry, western blot, and immunofluorescence studies were used to analyze the phenotypic characteristics of the cultured AF-MSC. Amniotic fluid-derived mesenchymal stem cells were successfully isolated and cultured from amniotic fluid. Flow cytometric analysis demonstrated that these cells expressed CD29 and CD44, while they did not express CD34. The expression of transcription factor Oct-4 was confirmed by western blot and immunofluorescence analysis. Using the adherence method, we developed a successful, reproducible protocol for the isolation of AF-MSC from amniotic fluid. The results of our phenotypic analysis revealed that the AF-MSC isolated in the present study were multipotent cells.
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Two cases of bacterial suppurative thyroiditis caused by Streptococcus anginosus.
Endocr. Pathol.
PUBLISHED: 02-26-2013
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Acute suppurative thyroiditis (AST) is a rare clinical condition. Streptococcus anginosus has a propensity of producing empyema in the head and neck. Here, we reported two cases of AST caused by S. anginosus. A 44-year-old man presented with anterior neck tender swelling and odynophagia for 12 days. He had thyrotoxicosis. He was initially diagnosed as thyroid cancer due to the misleading computed tomography report. Fine needle aspiration (FNA) yielded pus and neutrophils. S. anginosus was isolated from pus. After aspiration of abscess and treatment with sensitive antibiotics, he recovered uneventfully with 3 weeks treatment. He was euthyroid 3 months later. The other case is a 40-year-old women complained of fever and left neck swelling for 20 days. Magnetic resonance imaging showed left neck inflammatory changes. FNA revealed pus and inflammatory cells infiltration. She had moderately decreased level of thyroid-stimulating hormone (TSH). Blood cultures were positive for S. anginosus. After penicillin treatment, TSH level returned to normal range, and the nodule gradually resolved. She recovered uneventfully after 5 weeks treatment. S. anginosus has a previously unappreciated clinical niche in AST. Once AST is clinically concerned, FNA procedure should be performed as early as possible.
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Addition of cilostazol to conventional dual antiplatelet therapy reduces the risk of cardiac events and restenosis after drug-eluting stent implantation: a meta-analysis.
J Clin Pharmacol
PUBLISHED: 02-22-2013
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This meta-analysis was performed to compare the risk of cardiac events and restenosis between triple antiplatelet therapy (TAT, addition of cilostazol to aspirin and clopidogrel) and conventional dual antiplatelet therapy (DAT, aspirin and clopidogrel) in drug-eluting stents (DES) implantation patients. We performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation. Five clinical trials were involved in the study. TAT was associated with a 36% reduction in major adverse cardiac events (MACE; odds ratio (OR)?= 0.64; 95% confidence interval (CI)?= 0.51-0.81, P
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Preloading with atorvastatin before percutaneous coronary intervention in statin-naïve Asian patients with non-ST elevation acute coronary syndromes: A randomized study.
J Cardiol
PUBLISHED: 02-12-2013
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Data on atorvastatin pretreatment in Asian patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) are limited. However, there have been studies in other populations in Asia which demonstrated that statins can reduce the risk of periprocedural myocardial infarction (MI).
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Magnetic targeting enhances retrograde cell retention in a rat model of myocardial infarction.
Stem Cell Res Ther
PUBLISHED: 02-01-2013
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Retrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction.
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High PLTP activity is associated with depressed left ventricular systolic function.
Atherosclerosis
PUBLISHED: 01-29-2013
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Phospholipid transfer protein (PLTP) modulates lipoprotein metabolism and plays an important role in inflammation and oxidative stress. High PLTP activity is associated with atherosclerosis and its risk factors, which also predispose to left ventricular systolic (LV) dysfunction and/or congestive heart failure. However there are few data linking PLTP activity directly to LV function. According, we sought to determine the relation between PLTP activity and LV ejection fraction (EF) in a Chinese cohort of 732 patients referred for coronary angiography. Weak but significant correlations of PLTP activity levels were found with age (r = -0.09, p = 0.017), male gender (r = 0.09, p = 0.019), diabetes (r = 0.08, p = 0.036), TG (r = 0.11, p = 0.003), HDL-C (r = -0.18, p = <0.001), apo A (-0.30, p < 0.001) apo B (r = 0.20, p < 0.001), fibrinogen (r = 0.32, p < 0.001) and LVEF (r = -0.12, p = 0.003). Median PLTP activity levels were higher among patients with reduced than in normal LV systolic function (LVEF <50%) [26.7 pmol/microl/h (IQR 20.2, 38.6) vs. 19.9 pmol/microl/h (IQR 12.2, 31.0), p < 0.001]. There was a step-wise increase in median PLTP levels in patients with normal, mild, and moderate-severe degrees of LV dysfunction (19.9 pmol/microl/h vs. 25.1 pmol/microl/h vs. 34.7 pmol/microl/h, p < 0.001). Median PLTP activity levels were higher among patients with unstable rather than stable AP and non-CHD patients (25.9 pmol/microl/h vs 20.2 vs 21.9, p = 0.012). On multivariate analyzes, higher median PLTP activity levels were associated with depressed LV systolic function as a dichotomous variable and with lower LVEF as a continuous variable. In conclusion, higher PLTP activity is associated with depressed LV systolic function in a dose-dependent manner independent of coronary heart disease as well as to unstable CHD.
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Granulocyte colony-stimulating factor promotes atherosclerosis in high-fat diet rabbits.
Int J Mol Sci
PUBLISHED: 01-28-2013
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Granulocyte-colony stimulating factor (G-CSF) has been reported to improve the function of infarcted heart, but its effects on atherosclerosis are unclear. Here we examined the effects and the potential mechanisms in the high-fat diet rabbit model. Six-month-old male New Zealand white rabbits, fed a high-cholesterol diet or a normal diet for 10 weeks, were treated with vehicle or G-CSF. G-CSF increased lesion area in the thoracic aorta and the plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) at the early phase in the high-fat diet group. High-fat diet-induced arterial endothelium damage and apoptosis were greatly aggravated by G-CSF treatment. In vivo, G-CSF impaired apoptosis induced by oxidized low density lipoprotein (OX-LDL) but it had little effect on cultured endothelial cells (ECs) with vehicle treatment. Further research revealed that G-CSF promoted the upregulation of endothelin-1 (ET-1) and the downregulation of endothelial nitric oxide synthase (eNOS) of thoracic aortae induced by a high-fat diet. In vitro, the effects of G-CSF on expression of ET-1 and eNOS in cultured ECs were consistent with those in vivo. Our results suggested that G-CSF exacerbates lipid abnormity and endothelium damage in hyperlipidemia rabbits, thereby resulting in the deterioration of atherosclerosis and that the ET-1/eNOS system may regulate the progression.
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Naoxintong protects against atherosclerosis through lipid-lowering and inhibiting maturation of dendritic cells in LDL receptor knockout mice fed a high-fat diet.
Curr. Pharm. Des.
PUBLISHED: 01-28-2013
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Naoxintong (NXT), a Chinese Materia Medica standardized product, extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinennsis, Astragali Radix, is clinically effective in treating atherosclerosisrelated diseases. Here, we tested the hypothesis that the anti-atherosclerosis effects of NXT might be mediated by suppressing maturation of dendritic cells (DCs) in a mice model of atherosclerosis. LDLR(-/-) mice fed a high-fat diet were treated with placebo, NXT (0.7 g/kg/d, oral diet) or simvastatin (100mg/kg/d, oral diet) for 8 weeks, respectively. NXT treatment significantly reduced plasma triglyceride (112 ± 18 mg/dl vs. 192 ± 68 mg/dl, P<0.05) and total cholesterol (944 ± 158 mg/dl vs. 1387 ± 208 mg/dl, P<0.05) compared to placebo treatment. Vascular lesions were significantly smaller and macrophage content and amount of DCs in plaques were significantly less in NXT and simvastatin groups than in placebo group (all P<0.05). In addition, expressions of splenic DC membrane molecules (CD40, CD86 and CD80) and the plasma level of IL-12p70 were significantly lower in NXT and simvastatin groups than in placebo group. In conclusion, NXT protects against atherosclerosis through lipid-lowering and inhibiting DCs maturation in this mice model of atherosclerosis.
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Time course of current of injury is related to acute stability of active-fixation pacing leads in rabbits.
PLoS ONE
PUBLISHED: 01-24-2013
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Magnitude of current of injury (COI) consequent to pacemaker lead fixation is recognized as a predictor of acute lead stability. It is unclear whether dynamic monitoring of COI after lead fixation provides additional information beyond a single assessment performed at the time of fixation.
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Anti-inflammatory effects of arsenic trioxide eluting stents in a porcine coronary model.
Biomed Res Int
PUBLISHED: 01-16-2013
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Previous research from our group has demonstrated arsenic trioxide eluting stents significantly reduced neointimal area and thickness compared with bare metal stents. In the present study, the anti-inflammatory effects of arsenic trioxide in vitro and arsenic trioxide eluting stents in a porcine coronary model have been explored. Sixty-five pigs underwent placement of 139 oversized stents in the coronary arteries with histologic analysis, endothelial function analysis, and immunohistochemical and western blot analyses. Arsenic trioxide eluting stents effectively inhibited local inflammatory reactions, while no significant difference in endothelialization and endothelial function between arsenic trioxide eluting stents and bare metal stents was observed. Arsenic trioxide eluting stents favorably modulate neointimal formation due to less augmentation of early inflammatory reactions, and quick endothelialization of the stent surface, which might contribute to long-term safety and efficacy of drug eluting stents.
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MicroRNA-34a promotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2.
Curr. Pharm. Des.
PUBLISHED: 01-10-2013
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MicroRNA-34a (miR-34a) promotes apoptosis via down-regulating many anti-apoptotic proteins. Aldehyde dehydrogenase 2 (ALDH2) is an anti-apoptotic enzyme whose activity decline associates with myocardial injury. We tested hypothesis that miR-34a might play a pro-apoptotic role in myocardial infarction (MI) by down-regulating ALDH2. MiR-34a was highly increased while ALDH2 expression was decreased after experimental MI. Overexpression of miR-34a in neonatal rat cardiomyocyte could significantly enhance apoptosis and down-regulate ALDH2 expression. In 293 cells, luciferase reporter assay results demonstrated that ALDH2 was a direct target of miR-34a. Serum miR-34a levels in acute myocardial infarction (AMI) patients and rats were significantly higher than healthy subjects and sham rats. Our results proved that miR-34a could promote cardiomyocyte apoptosis via negatively regulating ALDH2 and circulating miR-34a was increased in the condition of MI. Thus, miR-34a may constitute a new therapeutic target and diagnostic marker for patients with MI.
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Regulation of p53 by jagged1 contributes to angiotensin II-induced impairment of myocardial angiogenesis.
PLoS ONE
PUBLISHED: 01-01-2013
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Angiotensin II (AngII) is a major contributor to the development of heart failure, however, the molecular and cellular mechanisms still remain elucidative. Inadequate angiogenesis in myocardium leads to transition from cardiac hypertrophy to dysfunction, this study was therefore conducted to examine the effects of AngII on myocardial angiogenesis and the underlying mechanisms. AngII treatment significantly impaired angiogenetic responses, which were determined by counting the capillaries either in matrigel formed by cultured cardiac microvascular endothelial cells (CMVECs) or in myocardium of mice and by measuring the in vitro and in vivo production of VEGF proteins, and stimulated accumulation and phosphorylation of cytosolic p53 which led to increases in phosphorylated p53 and decreases of hypoxia inducible factor (Hif-1) in nucleus. All of these cellular and molecular events induced by AngII in CEMCs and hearts of mice were largely reduced by a p53 inhibitor, pifithrin-? (PFT-?). Interestingly, AngII stimulated the upregulation of Jagged1, a ligand of Notch, but it didnt affect the expression of Delta-like 4 (Dll-4), another ligand of Notch. Inhibition of p53 by PFT-? partly abolished this effect of AngII. Further experiments showed that knockdown ofJagged1 by addition of siRNA to cultured CMVECs dramatically declined AngII-stimulated accumulation and phosphorylation of p53 in cytosol, upregulation of phosphorylated p53 and downregulation of Hif-1 expression in nucleus, decrease of VEGF production and impairment of capillary-like tube formation by the cells. Our data collectively suggest that AngII impairs myocardial angiogenetic responses through p53-dependent downregulation of Hif-1 which is regulated by Jagged1/Notch1 signaling.
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In vivo delivery of adenoviral vector containing interleukin-17 receptor a reduces cardiac remodeling and improves myocardial function in viral myocarditis leading to dilated cardiomyopathy.
PLoS ONE
PUBLISHED: 01-01-2013
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Th17 cells have been implicated in the pathogenesis of myocarditis. Interleukin (IL)-17A produced by Th17 cells is dispensable for viral myocarditis but essential for the progression to dilated cardiomyopathy (DCM). This study investigated whether the adenoviral transfer of the IL-17 receptor A reduces myocardial remodeling and dysfunction in viral myocarditis leading to DCM. In a mouse model of Coxsackievirus B3 (CVB3)-induced chronic myocarditis, the delivery of the adenovirus-containing IL-17 receptor A (Ad-IL17RA:Fc) reduced IL-17A production and decreased the number of Th17 cells in the spleen and heart, leading to the down-regulation of systemic TNF-? and IL-6 production. Cardiac function improved significantly in the Ad-IL17R:Fc- compared with the Ad-null-treated mice 3 months after the first CVB3 infection. Ad-IL17R:Fc reduced the left ventricle dilation and decreased the mortality in viral myocarditis, leading to DCM (56% in the Ad-IL17R:Fc versus 76% in the Ad-null group). The protective effects of Ad-IL17R-Fc on remodeling correlated with the attenuation of myocardial collagen deposition and the reduction of fibroblasts in CVB3-infected hearts, which was accompanied by the down-regulation of A distintegrin and metalloprotease with thrombospondin type 1 motifs (ADAMTS-1), Matrix metalloproteinase-2(MMP-2), and collagen subtypes I and III in the heart. Moreover, in cultured cardiac fibroblasts, IL-17A induced the expression of ADAMTS-1, MMP-2, and collagen subtypes I and III and increased the proliferation of fibroblasts. We determined that the delivery of IL-17-RA:Fc reduces cardiac remodeling, improves function, and decreases mortality in viral myocarditis leading to DCM, possibly by suppressing fibrosis. Therefore, the adenoviral transfer of the IL-17 receptor A may represent an alternative therapy for chronic viral myocarditis and its progression to DCM.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.