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Find video protocols related to scientific articles indexed in Pubmed.
Disturbed flow induces systemic changes in metabolites in mouse plasma: A metabolomics study using ApoE-/- mice with partial carotid ligation.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 11-08-2014
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Disturbed blood flow (d-flow) occurring in branched and curved arteries promotes endothelial dysfunction and atherosclerosis, in part by altering gene expression and epigenomic profiles in endothelial cells. While a systemic metabolic change is known to play a role in atherosclerosis, it is unclear whether it can be regulated by local d-flow. Here, we tested this hypothesis by carrying out a metabolomics study using blood plasma samples obtained from ApoE-/- mice that underwent a partial carotid ligation surgery to induce d-flow. Mice receiving sham ligation were used as a control. To study early metabolic changes, samples collected from 1 week after partial ligation when endothelial dysfunction occurs, but before atheroma develops were analyzed by high-resolution mass spectrometry. A metabolome-wide association study showed that 128 metabolites were significantly altered in the ligated mice compared to the sham group. Of these, sphingomyelin (SM; m/z 703.5747), a common mammalian cell membrane sphingolipid, was most significantly increased in the ligated mice. Eighteen and 41 of the 128 discriminatory metabolites were positively and negatively correlated with SM, respectively. The amino acids methionine and phenylalanine were increased by d-flow while phosphatidylcholine and phosphatidylethanolamine were decreased by d-flow, and these metabolites were correlated with SM. Other significantly affected metabolites included dietary and environmental agents. Pathway analysis showed that the metabolic changes of d-flow impacted broad functional networks. These results suggest that signaling from d-flow occurring in focal regions induce systemic metabolic changes associated with atherosclerosis.
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Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events.
J Am Heart Assoc
PUBLISHED: 10-25-2014
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Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown.
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Circulating CD34+ Progenitor Cells and Risk of Mortality in a Population with Coronary Artery Disease.
Circ. Res.
PUBLISHED: 10-18-2014
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Rationale: Low circulating progenitor cell (PC) numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. Objective: To investigate whether low numbers of PCs associate with a greater risk of mortality in a population at high cardiovascular risk. Methods and Results: Patients undergoing coronary angiography were recruited into two cohorts (1, n=502 and 2, n=403) over separate time periods. PCs were enumerated by flow cytometry as CD(45med+) blood mononuclear cells expressing CD34, with additional quantification of subsets co-expressing CD133, VEGFR2 and CXCR4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary endpoint of all-cause death. There was an inverse association between CD34+ and CD34+/CD133+ cell counts and risk of death in Cohort 1 (?=-0.92, p=0.043 and ?=-1.64, p=0.019, respectively) that was confirmed in Cohort 2 (?=-1.25, p=0.020 and ?=-1.81, p=0.015, respectively). Covariate adjusted HRs in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34+/CD133+ cell counts improved risk prediction metrics beyond standard risk factors. Conclusions: Reduced circulating PC counts, identified primarily as CD34+ mononuclear cells or its subset expressing CD133 are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction and cell selection for cell based therapies.
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Association of vitamin D status with mental stress-induced myocardial ischemia in patients with coronary artery disease.
Psychosom Med
PUBLISHED: 09-16-2014
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Mental stress-induced (MSIMI) or physical stress-induced (PSIMI) myocardial ischemia portends a worse prognosis in patients with coronary artery disease (CAD). Vitamin D insufficiency is associated with adverse cardiovascular outcomes, but its relationship to myocardial ischemia remains unclear. We hypothesized that vitamin D insufficiency will be associated with a higher prevalence of myocardial ischemia in patients with CAD.
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Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies.
PLoS ONE
PUBLISHED: 09-02-2014
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein (LDL) receptor. Mutations that block PCSK9 secretion reduce LDL-cholesterol and the incidence of myocardial infarction (MI). However, it remains unclear whether elevated plasma PCSK9 associates with coronary atherosclerosis (CAD) or more directly with rupture of the plaque causing MI.
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Sex and age differences in the association of depression with obstructive coronary artery disease and adverse cardiovascular events.
J Am Heart Assoc
PUBLISHED: 06-20-2014
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Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women.
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Circadian variation in vascular function and regenerative capacity in healthy humans.
J Am Heart Assoc
PUBLISHED: 05-17-2014
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Progenitor cells (PCs) are mobilized in response to vascular injury to effect regeneration and repair. Recruitment of PCs requires intact nitric oxide (NO) synthesis by endothelial cells, and their number and activity correlate with cardiovascular disease risk burden and future outcomes. Whereas cardiovascular vulnerability exhibits a robust circadian rhythm, the 24-hour variation of PCs and their inter-relation with vascular function remain unknown. We investigated the circadian variation of PCs and vascular function with the hypothesis that this will parallel the pattern observed for cardiovascular events (CVEs).
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Effects of storage-aged red blood cell transfusions on endothelial function in hospitalized patients.
Transfusion
PUBLISHED: 03-31-2014
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Clinical and animal studies indicate that transfusions of older stored red blood cells (RBCs) impair clinical outcomes as compared to fresh RBC transfusions. It has been suggested that this effect is due to inhibition of nitric oxide (NO)-mediated vasodilation after transfusion of older RBC units. However, to date this effect has not been identified in human transfusion recipients.
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Differences in vascular nitric oxide and endothelium-derived hyperpolarizing factor bioavailability in blacks and whites.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 03-27-2014
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Abnormalities in nitric oxide (NO) bioavailability have been reported in blacks. Whether there are differences in endothelium-derived hyperpolarizing factor (EDHF) in addition to NO between blacks and whites and how these affect physiological vasodilation remain unknown. We hypothesized that the bioavailability of vascular NO and EDHF, at rest and with pharmacological and physiological vasodilation, varies between whites and blacks.
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Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.
Hypertension
PUBLISHED: 03-10-2014
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Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (?=9.53; P<0.001), Ln glutathione (?=-5.4; P=0.002), and Eh glutathione (?=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (?=6.56; P=0.007), mitral regurgitation (?=4.52; P<0.001), statin use (?=-3.39; P=0.03), left ventricular ejection fraction (?=-0.26; P=0.003), and age (?=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (?50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.
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Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease.
Am. J. Cardiol.
PUBLISHED: 03-02-2014
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Mental stress-induced myocardial ischemia (MSIMI) has been associated with adverse prognosis in patients with coronary artery disease (CAD), but whether this is a uniform finding across different studies has not been described. We conducted a systematic review and meta-analysis of prospective studies examining the association between MSIMI and adverse outcome events in patients with stable CAD. We searched PubMed, EMBASE, Web of Science, and PsycINFO databases for English language prospective studies of patients with CAD who underwent standardized mental stress testing to determine presence of MSIMI and were followed up for subsequent cardiac events or total mortality. Our outcomes of interest were CAD recurrence, CAD mortality, or total mortality. A summary effect estimate was derived using a fixed-effects meta-analysis model. Only 5 studies, each with a sample size of <200 patients and fewer than 50 outcome events, met the inclusion criteria. The pooled samples comprised 555 patients with CAD (85% male) and 117 events with a range of follow-up from 35 days to 8.8 years. Pooled analysis showed that MSIMI was associated with a twofold increased risk of a combined end point of cardiac events or total mortality (relative risk 2.24, 95% confidence interval 1.59 to 3.15). No heterogeneity was detected among the studies (Q=0.39, I2=0.0%, p=0.98). In conclusion, although few selected studies have examined the association between MSIMI and adverse events in patients with CAD, all existing investigations point to approximately a doubling of risk. Whether this increased risk is generalizable to the CAD population at large and varies in patient subgroups warrant further investigation.
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Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET.
J Nucl Cardiol
PUBLISHED: 01-31-2014
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An impaired chronotropic response to exercise is an accepted risk marker but the relationship between heart rate reserve (HRR) with pharmacologic stress is less well-established. The primary aim of this analysis was to evaluate the prognostic significance of HRR in patients undergoing rest/stress myocardial perfusion positron emission tomography (PET) in estimating coronary artery disease (CAD) mortality.
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Combination of plaque burden, wall shear stress, and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability.
Atherosclerosis
PUBLISHED: 01-29-2014
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Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability.
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Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation.
Am. Heart J.
PUBLISHED: 01-27-2014
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Endothelial dysfunction is highly prevalent and associated with adverse outcomes among patients without obstructive coronary artery disease (CAD). Angiotensin II inhibition may improve endothelial function, but with continued treatment, "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone blockade further improves endothelial function.
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Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease.
J Nucl Cardiol
PUBLISHED: 01-20-2014
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Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD.
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Endothelium-derived hyperpolarizing factor mediates bradykinin-stimulated tissue plasminogen activator release in humans.
J. Vasc. Res.
PUBLISHED: 01-13-2014
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Bradykinin (BK) stimulates tissue plasminogen activator (t-PA) release from human endothelium. Although BK stimulates both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release remains unexplored. This study sought to determine the mechanisms of BK-stimulated t-PA release in the forearm vasculature of healthy human subjects.
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Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events: a systematic review and meta-analysis.
J. Am. Coll. Cardiol.
PUBLISHED: 01-07-2014
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The purpose of this analysis was to compare the association between variants at the chromosome 9p21 locus (Ch9p21) and risk of first versus subsequent coronary heart disease (CHD) events through systematic review and meta-analysis.
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Association between Vitamin D and Adiponectin and Its Relationship with Body Mass Index: The META-Health Study.
Front Public Health
PUBLISHED: 01-01-2014
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Low vitamin D and adiponectin levels are both associated with obesity and cardiovascular disease. Previous studies have indicated that vitamin D levels are directly associated with adiponectin, and that this association varies across body mass index (BMI) categories; stronger with increasing BMI. Few studies examined this association in African-Americans (AA), known to have lower levels of vitamin D and adiponectin, and in whites.
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Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death.
Genome Med
PUBLISHED: 01-01-2014
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Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.
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A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.
PLoS ONE
PUBLISHED: 01-01-2014
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Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2?=?-0.23), vascular stiffness (R2?=?-0.24), and central aortic pressure (R2?=?-0.19) and positively correlated with body mass index (R2?=?0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis.
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Sodium nitrite in patients with peripheral artery disease and diabetes mellitus: Safety, walking distance and endothelial function.
Vasc Med
PUBLISHED: 12-20-2013
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Nitrite stores decrease after exercise in patients with peripheral artery disease (PAD) and diabetes represents decreased nitric oxide (NO) bioavailability that may contribute to endothelial dysfunction and limit exercise duration. The primary objective of this placebo-controlled study was the safety and tolerability of multiple doses of oral sodium nitrite in patients with PAD, predominantly with diabetes, over a period of 10 weeks. The primary efficacy endpoint was endothelial flow-mediated dilatation (FMD) and secondary efficacy endpoints included a 6-minute walk test and quality of life assessment. Of the 55 subjects, the most common side effects attributed to sodium nitrite were a composite of headache and dizziness occurring in 21% with the 40 mg dose and 44% with the 80 mg dose. There was no clinically significant elevation of methemoglobin. FMD non-significantly worsened in the placebo and 40 mg groups, but was stable in the 80 mg group. Diabetic patients receiving 80 mg had significantly higher FMD compared with the placebo and 40 mg groups. There was no significant change in 6-minute walk test or quality of life parameters over time compared to placebo. In conclusion, sodium nitrite therapy is well tolerated in patients with PAD. The possible clinical benefit of sodium nitrite should be studied in a larger and fully powered trial.
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Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial.
JAMA
PUBLISHED: 11-20-2013
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Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown.
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Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress.
Psychosom Med
PUBLISHED: 10-25-2013
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Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress.
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Myocardial ischemia during mental stress: role of coronary artery disease burden and vasomotion.
J Am Heart Assoc
PUBLISHED: 10-23-2013
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Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse prognosis in patients with coronary artery disease (CAD), yet the mechanisms underlying this phenomenon remain unclear. We hypothesized that compared with exercise/pharmacological stress-induced myocardial ischemia (PSIMI) that is secondary to the atherosclerotic burden of CAD, MSIMI is primarily due to vasomotor changes.
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Coronary heart disease alters intercellular communication by modifying microparticle-mediated microRNA transport.
FEBS Lett.
PUBLISHED: 07-19-2013
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Coronary heart disease (CHD) is characterized by abnormal intercellular communication and circulating microRNAs (miRNAs) are likely involved in this process. Here, we show that CHD was associated with changes in the transport of circulating miRNA, particularly decreased miRNA enrichment in microparticles (MPs). Additionally, MPs from CHD patients were less efficient at transferring miRNA to cultured HUVECs, which correlated with their diminished capacity to bind developmental endothelial locus-1 (Del-1). In summary, CHD was associated with distinct changes in circulating miRNA transport and these changes may contribute to the abnormal intercellular communication that underlies CHD initiation and progression.
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Effect of meditation on endothelial function in black americans with metabolic syndrome: a randomized trial.
Psychosom Med
PUBLISHED: 06-20-2013
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Psychological stress may play a role in metabolic syndrome. A consequence of metabolic syndrome is endothelial dysfunction, which is also influenced by psychological stress. We sought to compare the effect of consciously resting meditation (CRM), a sound based meditation, with a control intervention of health education (HE) on endothelial function in the setting of metabolic syndrome.
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Vitamin D and cardiovascular disease: is the evidence solid?
Eur. Heart J.
PUBLISHED: 06-09-2013
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Vitamin D deficiency, prevalent in 30-50% of adults in developed countries, is largely due to inadequate cutaneous production that results from decreased exposure to sunlight, and to a lesser degree from low dietary intake of vitamin D. Serum levels of 25-hydroxyvitamin D (25-OH D) <20 ng/mL indicate vitamin D deficiency and levels >30 ng/mL are considered optimal. While the endocrine functions of vitamin D related to bone metabolism and mineral ion homoeostasis have been extensively studied, robust epidemiological evidence also suggests a close association between vitamin D deficiency and cardiovascular morbidity and mortality. Experimental studies have demonstrated novel actions of vitamin D metabolites on cardiomyocytes, and endothelial and vascular smooth muscle cells. Low 25-OH D levels are associated with left ventricular hypertrophy, vascular dysfunction, and renin-angiotensin system activation. Despite a large body of experimental, cross-sectional, and prospective evidence implicating vitamin D deficiency in the pathogenesis of cardiovascular disease, a causal relationship remains to be established. Moreover, the cardiovascular benefits of normalizing 25-OH D levels in those without renal disease or hyperparathyroidism have not been established, and questions of an epiphenomenon where vitamin D status merely reflects a classic risk burden have been raised. Randomized trials of vitamin D replacement employing cardiovascular endpoints will provide much needed evidence for determining its role in cardiovascular protection.
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Monoamine oxidase A genotype, childhood trauma, and subclinical atherosclerosis: a twin study.
Psychosom Med
PUBLISHED: 05-30-2013
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A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated in neuropsychiatric disorders and also moderates the association between early-life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma, and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis.
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Racial differences in arterial stiffness and microcirculatory function between Black and White Americans.
J Am Heart Assoc
PUBLISHED: 04-10-2013
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Compared with whites, black Americans suffer from a disproportionate burden of cardiovascular disease (CVD). We hypothesized that racial differences in the prevalence of CVD could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden.
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Progenitor Cell Therapy to Treat Acute Myocardial Infarction: The Promise of High-Dose Autologous CD34(+) Bone Marrow Mononuclear Cells.
Stem Cells Int
PUBLISHED: 03-18-2013
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ST elevation myocardial infarction (STEMI) is associated with an increased risk for congestive heart failure and long-term mortality despite the widespread use of thrombolysis and catheter-based revascularization. The need for improved post-STEMI therapies has led to a surge of novel therapeutics, especially regenerative approaches using autologous mononuclear cells. Indeed, the past decade has been marked by a number of human trials studying the safety and efficacy of progenitor cell delivery in the post-STEMI setting. While a variety of cell types and delivery techniques have been utilized, directed therapy to the infarct-related artery has been the most widely used approach. From over 1300 subjects randomized in these studies, there is sufficient evidence to conclude that cell therapy after STEMI is uniformly safe, while the efficacy of this intervention for improving outcomes is less clear. Recent meta-analyses have highlighted the importance of both timing of cell delivery, as well as the type, quantity, and mobility of delivered cells as determinants of response. Here, we show the case in which higher doses of CD34(+) cells, which are more potent in terms of their migratory capacity, offer the best hope for preserving cardiac function following STEMI.
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Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome.
BMC Med. Genet.
PUBLISHED: 09-29-2011
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Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated.
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Substitution of standard soybean oil with olive oil-based lipid emulsion in parenteral nutrition: comparison of vascular, metabolic, and inflammatory effects.
J. Clin. Endocrinol. Metab.
PUBLISHED: 08-10-2011
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Soybean oil-based lipid emulsions are the only Food and Drug Administration-approved lipid formulation for clinical use in parenteral nutrition (PN). Recently concerns with its use have been raised due to the proinflammatory effects that may lead to increased complications because they are rich in ?-6 polyunsaturated fatty acids.
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Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease.
Circulation
PUBLISHED: 07-25-2011
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Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression.
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Intravascular imaging findings in severe coronary vasospasm.
J Cardiovasc Med (Hagerstown)
PUBLISHED: 06-29-2011
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Appropriate diagnosis of patients with chest pain and no significant angiographic coronary artery disease remains challenging. We present the case of a 65-year-old woman with recurrent chest pain that was triggered by exertion as well as emotional stress. She underwent coronary angiography and intravascular ultrasound which demonstrated no atherosclerosis. Coronary flow reserve assessment was also normal suggesting no significant microvascular disease. Intracoronary infusion of acetylcholine, however, resulted in an increase in blood velocity and epicardial vasoconstriction, confirmed by chest pain, electrocardiogram changes and complete closure of a coronary artery by angiography, suggesting the diagnosis of coronary vasospasm or variant angina. This report highlights the importance of considering vasoconstriction when markedly increased blood velocity is observed in response to acetylcholine.
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Association between depression and inflammation--differences by race and sex: the META-Health study.
Psychosom Med
PUBLISHED: 06-28-2011
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To test whether the association between depression and inflammation differs by race and sex. Depressive symptoms have been associated with higher levels of C-reactive protein (CRP). However, few studies have examined this association in samples including a significant number of African Americans, or examined whether the association differs by race and sex.
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Characterization of mechanical dyssynchrony measured by gated single photon emission computed tomography phase analysis after acute ST-elevation myocardial infarction.
J Nucl Cardiol
PUBLISHED: 06-04-2011
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Left ventricular dyssynchrony is an adverse consequence of ST-elevation myocardial infarction (STEMI) and bears an unfavorable prognosis. Mechanical dyssynchrony as measured by phase analysis from gated single photon emission computed tomography (GSPECT) correlates well with other imaging methods of assessing dyssynchrony but has not been studied in STEMI. We hypothesized that systolic dyssynchrony as measured by GSPECT would correlate with adverse remodeling after STEMI.
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Endothelium-derived hyperpolarizing factor determines resting and stimulated forearm vasodilator tone in health and in disease.
Circulation
PUBLISHED: 05-09-2011
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We assessed the contribution of endothelium-derived hyperpolarizing factors to resting and agonist-stimulated vasodilator tone in health and disease. Tetraethylammonium chloride (TEA) was used to inhibit K(+)(Ca) channel activation and fluconazole was used to inhibit cytochrome P450 2C9-mediated epoxyeicosatrienoic acid synthesis. We hypothesized that endothelium-derived hyperpolarizing factors contribute to resting vascular tone by K(+)(Ca) channel activation and epoxyeicosatrienoic acid release and that endothelium-derived hyperpolarizing factors compensate for reduced nitric oxide bioavailability at rest and with endothelium-dependent vasodilators.
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Insufficient nitric oxide bioavailability: a hypothesis to explain adverse effects of red blood cell transfusion.
Transfusion
PUBLISHED: 04-19-2011
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While transfusion of red blood cells (RBCs) is effective at preventing morbidity and mortality in anemic patients, studies have indicated that some RBC components have functional defects ("RBC storage lesions") that may actually cause adverse events when transfused. For example, in some studies patients transfused with RBCs stored more than 14 days have had statistically worse outcomes than those receiving "fresher" RBC units. Recipient-specific factors may also contribute to the occurrence of these adverse events. Unfortunately, these events have been difficult to investigate because up to now they have existed primarily as "statistical occurrences" of increased morbidity and mortality in large data sets. There are currently no clinical or laboratory methods to detect or study them in individual transfusion recipients. We propose a unifying hypothesis, centered on insufficient nitric oxide bioavailability (INOBA), to explain the increased morbidity and mortality observed in some patients after RBC transfusion. In this model, variables associated with RBC units (storage time; 2,3-diphosphoglycerate acid concentration) and transfusion recipients (endothelial dysfunction) collectively lead to changes in nitric oxide (NO) levels in vascular beds. Under certain circumstances, these variables are "aligned" such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow, and insufficient O(2) delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. If the key tenets of the INOBA hypothesis are confirmed, it may lead to improved transfusion methods including altered RBC storage and/or processing conditions, novel transfusion recipient screening methods, and improved RBC-recipient matching.
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Role of interleukin 17 in inflammation, atherosclerosis, and vascular function in apolipoprotein e-deficient mice.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 04-07-2011
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Interleukin 17A (IL17A) is involved in many inflammatory processes, but its role in atherosclerosis remains controversial. We examined the role of IL17A in mouse and human atherosclerosis.
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The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin.
J Clin Lipidol
PUBLISHED: 04-01-2011
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Atherogenic risk in subjects with metabolic syndrome is partly mediated by increased oxidative stress and subsequent endothelial dysfunction. Clinical trials have demonstrated differences in outcomes between subjects receiving lipophilic statins (atorvastatin) compared with hydrophilic statins (pravastatin). However, whether these findings are attributable to differences in the doses administered or to nonlipid-lowering pleiotropic effects of statins on oxidative stress and vascular function remains unknown. We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.
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Inflammation is related to coronary flow reserve detected by positron emission tomography in asymptomatic male twins.
J. Am. Coll. Cardiol.
PUBLISHED: 03-12-2011
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This study sought to examine the relationship between inflammation and coronary microvascular function in asymptomatic individuals using positron emission tomography (PET) and assessment of coronary flow reserve (CFR).
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A Temporal Abstraction-based Extract, Transform and Load Process for Creating Registry Databases for Research.
AMIA Summits Transl Sci Proc
PUBLISHED: 03-07-2011
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In the CTSA era there is great interest in aggregating and comparing populations across institutions. These sites likely represent data differently in their clinical data warehouses and other databases. Clinical data warehouses frequently are structured in a generalized way that supports many constituencies. For research, there is a need to transform these heterogeneous data into a shared representation, and to perform categorization and interpretation to optimize the data representation for investigators. We are addressing this need by extending an existing temporal abstraction-based clinical database query system, PROTEMPA. The extended system allows specifying data types of interest in federated databases, extracting the data into a shared representation, transforming it through categorization and interpretation, and loading it into a registry database that can be refreshed. Such a registrys access control, data representation and query tools can be tailored to the needs of research while keeping local databases as the source of truth.
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Endothelium-derived hyperpolarizing factor and vascular function.
Cardiol Res Pract
PUBLISHED: 03-07-2011
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Endothelial function refers to a multitude of physiological processes that maintain healthy homeostasis of the vascular wall. Exposure of the endothelium to cardiac risk factors results in endothelial dysfunction and is associated with an alteration in the balance of vasoactive substances produced by endothelial cells. These include a reduction in nitric oxide (NO), an increase in generation of potential vasoconstrictor substances and a potential compensatory increase in other mediators of vasodilation. The latter has been surmised from data demonstrating persistent endothelium-dependent vasodilatation despite complete inhibition of NO and prostaglandins. This remaining non-NO, non-prostaglandin mediated endothelium-dependent vasodilator response has been attributed to endothelium-derived hyperpolarizing factor/s (EDHF). Endothelial hyperpolarization is likely due to several factors that appear to be site and species specific. Experimental studies suggest that the contribution of the EDHFs increase as the vessel size decreases, with a predominance of EDHF activity in the resistance vessels, and a compensatory up-regulation of hyperpolarization in states characterized by reduced NO availability. Since endothelial dysfunction is a precursor for atherosclerosis development and its magnitude is a reflection of future risk, then the mechanisms underlying endothelial dysfunction need to be fully understood, so that adequate therapeutic interventions can be designed.
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The role of plasma aminothiols in the prediction of coronary microvascular dysfunction and plaque vulnerability.
Atherosclerosis
PUBLISHED: 02-27-2011
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Although oxidative stress is considered a key pathogenic step in mediating vascular dysfunction and atherosclerosis development, their association has not been evaluated in human coronary circulation in vivo. Accordingly, we hypothesized that higher oxidative stress would be associated with abnormal coronary epicardial structure and microvascular function.
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CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent.
Am. Heart J.
PUBLISHED: 02-24-2011
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the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells.
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MicroRNA Expression Profile in CAD Patients and the Impact of ACEI/ARB.
Cardiol Res Pract
PUBLISHED: 02-21-2011
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Coronary artery disease (CAD) is the largest killer of males and females in the United States. There is a need to develop innovative diagnostic markers for this disease. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in important cellular processes, and we hypothesized that the miRNA expression profile would be altered in whole blood samples of patients with CAD. We performed a microarray analysis on RNA from the blood of 5 male subjects with CAD and 5 healthy subjects (mean age 53 years). Subsequently, we performed qRT-PCR analysis of miRNA expression in whole blood of another 10 patients with CAD and 15 healthy subjects. We identified 11 miRNAs that were significantly downregulated in CAD subjects (P < .05). Furthermore, we found an association between ACEI/ARB use and downregulation of several miRNAs that was independent of the presence of significant CAD. In conclusion, we have identified a distinct miRNA signature in whole blood that discriminates CAD patients from healthy subjects. Importantly, medication use may significantly alter miRNA expression. These findings may have significant implications for identifying and managing individuals that either have CAD or are at risk of developing the disease.
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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
Heribert Schunkert, Inke R König, Sekar Kathiresan, Muredach P Reilly, Themistocles L Assimes, Hilma Holm, Michael Preuss, Alexandre F R Stewart, Maja Barbalic, Christian Gieger, Devin Absher, Zouhair Aherrahrou, Hooman Allayee, David Altshuler, Sonia S Anand, Karl Andersen, Jeffrey L Anderson, Diego Ardissino, Stephen G Ball, Anthony J Balmforth, Timothy A Barnes, Diane M Becker, Lewis C Becker, Klaus Berger, Joshua C Bis, S Matthijs Boekholdt, Eric Boerwinkle, Peter S Braund, Morris J Brown, Mary Susan Burnett, Ian Buysschaert, , John F Carlquist, Li Chen, Sven Cichon, Veryan Codd, Robert W Davies, George Dedoussis, Abbas Dehghan, Serkalem Demissie, Joseph M Devaney, Patrick Diemert, Ron Do, Angela Doering, Sandra Eifert, Nour Eddine El Mokhtari, Stephen G Ellis, Roberto Elosua, James C Engert, Stephen E Epstein, Ulf de Faire, Marcus Fischer, Aaron R Folsom, Jennifer Freyer, Bruna Gigante, Domenico Girelli, Solveig Gretarsdottir, Vilmundur Gudnason, Jeffrey R Gulcher, Eran Halperin, Naomi Hammond, Stanley L Hazen, Albert Hofman, Benjamin D Horne, Thomas Illig, Carlos Iribarren, Gregory T Jones, J Wouter Jukema, Michael A Kaiser, Lee M Kaplan, John J P Kastelein, Kay-Tee Khaw, Joshua W Knowles, Genovefa Kolovou, Augustine Kong, Reijo Laaksonen, Diether Lambrechts, Karin Leander, Guillaume Lettre, Mingyao Li, Wolfgang Lieb, Christina Loley, Andrew J Lotery, Pier M Mannucci, Seraya Maouche, Nicola Martinelli, Pascal P McKeown, Christa Meisinger, Thomas Meitinger, Olle Melander, Pier Angelica Merlini, Vincent Mooser, Thomas Morgan, Thomas W Mühleisen, Joseph B Muhlestein, Thomas Münzel, Kiran Musunuru, Janja Nahrstaedt, Christopher P Nelson, Markus M Nöthen, Oliviero Olivieri, Riyaz S Patel, Chris C Patterson, Annette Peters, Flora Peyvandi, Liming Qu, Arshed A Quyyumi, Daniel J Rader, Loukianos S Rallidis, Catherine Rice, Frits R Rosendaal, Diana Rubin, Veikko Salomaa, M Lourdes Sampietro, Manj S Sandhu, Eric Schadt, Arne Schäfer, Arne Schillert, Stefan Schreiber, Jürgen Schrezenmeir, Stephen M Schwartz, David S Siscovick, Mohan Sivananthan, Suthesh Sivapalaratnam, Albert Smith, Tamara B Smith, Jaapjan D Snoep, Nicole Soranzo, John A Spertus, Klaus Stark, Kathy Stirrups, Monika Stoll, W H Wilson Tang, Stephanie Tennstedt, Gudmundur Thorgeirsson, Gudmar Thorleifsson, Maciej Tomaszewski, André G Uitterlinden, Andre M van Rij, Benjamin F Voight, Nick J Wareham, George A Wells, H-Erich Wichmann, Philipp S Wild, Christina Willenborg, Jaqueline C M Witteman, Benjamin J Wright, Shu Ye, Tanja Zeller, Andreas Ziegler, Francois Cambien, Alison H Goodall, L Adrienne Cupples, Thomas Quertermous, Winfried März, Christian Hengstenberg, Stefan Blankenberg, Willem H Ouwehand, Alistair S Hall, Panos Deloukas, John R Thompson, Kari Stefansson, Robert Roberts, Unnur Thorsteinsdottir, Christopher J O'Donnell, Ruth McPherson, Jeanette Erdmann, Nilesh J Samani.
Nat. Genet.
PUBLISHED: 02-10-2011
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We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans.
J. Am. Coll. Cardiol.
PUBLISHED: 01-31-2011
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The primary objective of this study was to elucidate mechanisms underlying the link between vitamin D status and cardiovascular disease by exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established marker of vitamin D status, and vascular function in healthy adults.
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A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry.
J. Hum. Genet.
PUBLISHED: 01-27-2011
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A 58 kb region on chromosome 9p21.3 has consistently shown strong association with coronary artery disease (CAD) in multiple genome-wide association studies in populations of European and East Asian ancestry. In this study, we sought to further characterize the role of genetic variants in 9p21.3 in African American individuals. Apparently healthy African American siblings (n = 548) of patients with documented CAD < 60 years of age were genotyped and followed for incident CAD for up to 17 years. Tests of association for 86 single-nucleotide polymorphisms (SNPs) across the 9p21.3 region in a generalized estimating equation logistic framework under an additive model adjusting for traditional risk factors, family, follow-up time and population stratification were performed. A single SNP within the CDKN2B gene met stringent criteria for statistical significance, including permutation-based evaluations. This variant, rs3217989, was common (minor allele (G) frequency 0.242), conveyed protection against CAD (odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.07 to 0.50, P = 0.0008) and was replicated in a combined analysis of two additional case/control studies of prevalent CAD/MI in African Americans (n = 990, P = 0.024, OR = 0.779, 95% CI: 0.626-0.968). This is the first report of a CAD association signal in a population of African ancestry with a common variant within the CDKN2B gene, independent from previous findings in European and East Asian ancestry populations. The findings demonstrate a significant protective effect against incident CAD in African American siblings of persons with premature CAD, with replication in a combination of two additional African American cohorts.
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Oxidative stress is associated with impaired arterial elasticity.
Atherosclerosis
PUBLISHED: 01-11-2011
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Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans.
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Effects of smoking on coronary microcirculatory function: a twin study.
Atherosclerosis
PUBLISHED: 01-06-2011
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In asymptomatic smokers, coronary microcirculatory dysfunction, assessed by coronary flow reserve (CFR), is an early indicator of cardiovascular risk. Inflammation and oxidative stress may be the mechanisms through which smoking affects the microvasculature.
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Stem cells in cardiovascular disease.
Med Arh
PUBLISHED: 12-07-2010
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Advances in stem cell biology over the past decade have fueled interest in new therapies for acute and chronic cardiovascular diseases. Pre-clinical work with a variety of cell types has suggested efficacy in improving ischemia and ventricular function, although mechanisms of effect remain to be fully explained. Human studies using certain cell types have shown modest clinical efficacy, while the safety of these experimental therapies supports continuing patient-oriented research.
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Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 10-05-2010
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We compared the effects of high and low oral and intravenous (iv) fat load on blood pressure (BP), endothelial function, autonomic nervous system, and oxidative stress in obese healthy subjects. Thirteen obese subjects randomly received five 8-h infusions of iv saline, 20 (32 g, low iv fat) or 40 ml/h intralipid (64 g, high iv fat), and oral fat load at 32 (low oral) or 64 g (high oral). Systolic BP increased by 14 ± 10 (P = 0.007) and 12 ± 9 mmHg (P = 0.007) after low and high iv lipid infusions and by 13 ± 17 (P = 0.045) and 11 ± 11 mmHg (P = 0.040) after low and high oral fat loads, respectively. The baseline flow-mediated dilation was 9.4%, and it decreased by 3.8 ± 2.1 (P = 0.002) and 4.1 ± 3.1% (P < 0.001) after low and high iv lipid infusion and by 3.8 ± 1.8 (P = 0.002) and 5.0 ± 2.5% (P < 0.001) after low and high oral fat load, respectively. Oral and iv fat load stimulated oxidative stress, increased heart rate, and decreased R-R interval variability. Acute iv fat load decreased blood glucose by 6-10 mg/dl (P < 0.05) without changes in insulin concentration, whereas oral fat increased plasma insulin by 3.7-4.0 ?U/ml (P < 0.01) without glycemic variations. Intravenous saline and both oral and iv fat load reduced leptin concentration from baseline (P < 0.01). In conclusion, acute fat load administered orally or intravenously significantly increased blood pressure, altered endothelial function, and activated sympathetic nervous system by mechanisms not likely depending on changes in leptin, glucose, and insulin levels in obese healthy subjects. Thus, fat load, independent of its source, has deleterious hemodynamic effects in obese subjects.
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The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease.
Eur. Heart J.
PUBLISHED: 08-20-2010
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we tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores.
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Shear stress and plaque development.
Expert Rev Cardiovasc Ther
PUBLISHED: 04-20-2010
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Although traditional cardiovascular risk factors prime the soil for atherogenesis systemically, atherosclerosis primarily occurs in a site-specific manner with a predilection towards the inner wall of curvatures and outer wall of bifurcations with sparing of flow-dividers. Wall shear stress is a frictional force exerted parallel to the vessel wall that leads to alteration of the endothelial phenotype, endothelial cell signaling, gene and protein expression leading to a proinflammatory phenotype, reduced nitric oxide availability and disruption of the extracellular matrix, which in turn leads to plaque development. Clinical and experimental data are emerging that suggest the pathobiology associated with abnormal wall shear stress results in atherosclerotic plaque development and progression.
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FOS expression in blood as a LDL-independent marker of statin treatment.
Atherosclerosis
PUBLISHED: 03-18-2010
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The expression of FOS, a gene critical for monocyte and macrophage function, can be inhibited by statins through the disruption of a cholesterol-independent signaling pathway. In this pilot study, we hypothesized that blood FOS mRNA levels will be sensitive to statin treatment independent of LDL cholesterol levels.
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.
Solveig Gretarsdottir, Annette F Baas, Gudmar Thorleifsson, Hilma Holm, Martin den Heijer, Jean-Paul P M de Vries, Steef E Kranendonk, Clark J A M Zeebregts, Steven M van Sterkenburg, Robert H Geelkerken, Andre M van Rij, Michael J A Williams, Albert P M Boll, Jelena P Kostic, Adalbjorg Jonasdottir, Aslaug Jonasdottir, G Bragi Walters, Gisli Masson, Patrick Sulem, Jona Saemundsdottir, Magali Mouy, Kristinn P Magnusson, Gerard Tromp, James R Elmore, Natzi Sakalihasan, Raymond Limet, Jean-Olivier Defraigne, Robert E Ferrell, Antti Ronkainen, Ynte M Ruigrok, Cisca Wijmenga, Diederick E Grobbee, Svati H Shah, Christopher B Granger, Arshed A Quyyumi, Viola Vaccarino, Riyaz S Patel, A Maziar Zafari, Allan I Levey, Harland Austin, Domenico Girelli, Pier Franco Pignatti, Oliviero Olivieri, Nicola Martinelli, Giovanni Malerba, Elisabetta Trabetti, Lewis C Becker, Diane M Becker, Muredach P Reilly, Daniel J Rader, Thomas Mueller, Benjamin Dieplinger, Meinhard Haltmayer, Sigitas Urbonavicius, Bengt Lindblad, Anders Gottsäter, Eleonora Gaetani, Roberto Pola, Philip Wells, Marc Rodger, Melissa Forgie, Nicole Langlois, Javier Corral, Vicente Vicente, Jordi Fontcuberta, Francisco España, Niels Grarup, Torben Jørgensen, Daniel R Witte, Torben Hansen, Oluf Pedersen, Katja K Aben, Jacqueline de Graaf, Suzanne Holewijn, Lasse Folkersen, Anders Franco-Cereceda, Per Eriksson, David A Collier, Hreinn Stefansson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Einar M Valdimarsson, Hulda B Magnadottir, Sigurlaug Sveinbjörnsdóttir, Isleifur Olafsson, Magnus Karl Magnusson, Robert Palmason, Vilhelmina Haraldsdottir, Karl Andersen, Pall T Onundarson, Gudmundur Thorgeirsson, Lambertus A Kiemeney, Janet T Powell, David J Carey, Helena Kuivaniemi, Jes S Lindholt, Gregory T Jones, Augustine Kong, Jan D Blankensteijn, Stefan E Matthiasson, Unnur Thorsteinsdottir, Kari Stefansson.
Nat. Genet.
PUBLISHED: 02-24-2010
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We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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Major depression and coronary flow reserve detected by positron emission tomography.
Arch. Intern. Med.
PUBLISHED: 10-14-2009
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Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue.
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Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene.
Psychosom Med
PUBLISHED: 07-21-2009
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To assess whether genetic variants involved in inflammation play a role in the sex difference in depression. Depression is, in part, genetically determined and inflammation has been implicated. Women are twice as likely to develop depression as men.
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Variability of carotid artery measurements on 3-Tesla MRI and its impact on sample size calculation for clinical research.
Int J Cardiovasc Imaging
PUBLISHED: 04-30-2009
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Carotid MRI measurements are increasingly being employed in research studies for atherosclerosis imaging. The majority of carotid imaging studies use 1.5 T MRI. Our objective was to investigate intra-observer and inter-observer variability in carotid measurements using high resolution 3 T MRI. We performed 3 T carotid MRI on 10 patients (age 56 +/- 8 years, 7 male) with atherosclerosis risk factors and ultrasound intima-media thickness > or =0.6 mm. A total of 20 transverse images of both right and left carotid arteries were acquired using T2 weighted black-blood sequence. The lumen and outer wall of the common carotid and internal carotid arteries were manually traced; vessel wall area, vessel wall volume, and average wall thickness measurements were then assessed for intra-observer and inter-observer variability. Pearson and intraclass correlations were used in these assessments, along with Bland-Altman plots. For inter-observer variability, Pearson correlations ranged from 0.936 to 0.996 and intraclass correlations from 0.927 to 0.991. For intra-observer variability, Pearson correlations ranged from 0.934 to 0.954 and intraclass correlations from 0.831 to 0.948. Calculations showed that inter-observer variability and other sources of error would inflate sample size requirements for a clinical trial by no more than 7.9%, indicating that 3 T MRI is nearly optimal in this respect. In patients with subclinical atherosclerosis, 3 T carotid MRI measurements are highly reproducible and have important implications for clinical trial design.
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Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease.
Am. Heart J.
PUBLISHED: 04-12-2009
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We hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF) administration will be safe and will improve endothelial dysfunction and exercise capacity by mobilizing progenitor cells in patients with peripheral arterial disease (PAD).
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Intravenous intralipid-induced blood pressure elevation and endothelial dysfunction in obese African-Americans with type 2 diabetes.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-31-2009
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Increased free fatty acids (FFAs) are leading candidates in the pathogenesis of insulin resistance and hypertension in obese subjects. We evaluated the effect of sustained elevations of FFA on blood pressure, endothelial function, insulin secretion, inflammatory markers, and renin-angiotensin system.
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Impact of spironolactone on endothelial function in patients with single ventricle heart.
Congenit Heart Dis
PUBLISHED: 02-12-2009
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Mid-term survivors of the Fontan procedure are at risk for progressive heart failure, and endothelial dysfunction is thought to contribute to this process. Aldosterone antagonism has been shown to improve survival in adults with heart failure and the effects are mediated in part by changes in endothelial function. In the present study, we sought to determine if a short course of spironolactone improves endothelial function and alters serum cytokine profiles in adolescents and adults with single ventricle heart.
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
Nat. Genet.
PUBLISHED: 01-05-2009
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Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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Exercise pressor response and arterial baroreflex unloading during exercise in chronic kidney disease.
J. Appl. Physiol.
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Patients with chronic kidney disease (CKD) have poor exercise capacity, which contributes to cardiovascular risk. We sought to determine whether patients with stage 2 or stage 3 CKD have an augmented blood pressure (BP) response during exercise, and if so, whether overactivation of the sympathetic nervous system (SNS) during exercise might play a role. In 13 patients with CKD and hypertension and 13 controls with hypertension, we measured hemodynamics and muscle sympathetic nerve activity (MSNA) during the following maneuvers: low-level rhythmic handgrip (RHG 20%), which primarily stimulates mechanoreceptors, and moderate static handgrip exercise (SHG 30%) followed by posthandgrip circulatory arrest (PHGCA), which isolates metaboreceptors. During baseline studies, patients with CKD had significantly greater increases in mean arterial pressure (MAP) during SHG 30% (P = 0.045), RHG 20% (P = 0.031), and PHGCA (P = 0.043); however, the MSNA response was not augmented in patients with CKD compared with controls. We hypothesized that an augmented SNS response during exercise might be revealed in CKD if arterial baroreflex constraint was equalized using nitroprusside (NTP). These exercise maneuvers were repeated in patients with CKD during NTP infusion to equalize the BP response between groups, thereby relieving baroreflex-mediated suppression of SNS activity. With NTP infusion, patients with CKD had significantly increased MSNA responses during SHG 30% (P = 0.0044), and RHG 20% (P = 0.0064), but not during PHGCA (P > 0.05), suggesting increased reflex activation of the SNS during exercise, which may be mediated by mechanoreceptors but not metaboreceptors. Patients with CKD have an exaggerated BP response during rhythmic and static exercise with underlying SNS overactivation that is revealed during arterial baroreflex unloading during exercise.
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Association of coronary wall shear stress with atherosclerotic plaque burden, composition, and distribution in patients with coronary artery disease.
J Am Heart Assoc
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Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition.
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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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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.