JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Ideal cardiovascular health: associations with biomarkers and subclinical disease and impact on incidence of cardiovascular disease in the framingham offspring study.
Circulation
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
The American Heart Association Cardiovascular Health score (CVH score) is inversely associated with cardiovascular disease (CVD) incidence, but the mechanisms underlying this association warrant exploration.
Related JoVE Video
Biomarkers of cardiovascular stress and subclinical atherosclerosis in the community.
Clin. Chem.
PUBLISHED: 09-18-2014
Show Abstract
Hide Abstract
Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described.
Related JoVE Video
Targeting post-infarct inflammation by PET imaging: comparison of (68)Ga-citrate and (68)Ga-DOTATATE with (18)F-FDG in a mouse model.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 08-12-2014
Show Abstract
Hide Abstract
?: Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. (18)F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by (68)Ga-citrate and somatostatin receptor binding by (68)Ga-DOTATATE.
Related JoVE Video
Clinically relevant strategies for lowering cardiomyocyte glucose uptake for (18)F-FDG imaging of myocardial inflammation in mice.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 08-02-2014
Show Abstract
Hide Abstract
Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols.
Related JoVE Video
Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy.
Int. J. Cardiol.
PUBLISHED: 01-12-2014
Show Abstract
Hide Abstract
No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).
Related JoVE Video
Thrombomodulin's lectin-like domain reduces myocardial damage by interfering with HMGB1-mediated TLR2 signalling.
Cardiovasc. Res.
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
Thrombomodulin (TM), via its lectin-like domain (LLD), exhibits anti-inflammatory properties partly by sequestering the pro-inflammatory cytokine, high-mobility group box 1 (HMGB1). Since myocardial damage after ischaemia and reperfusion is mediated by inflammation, we evaluated the cardioprotective effects of the LLD of TM. Using an in vivo mouse model of transient ischaemia and in vitro models of cardiomyocyte hypoxia, we assessed the ability of the LLD to suppress HMGB1-mediated activation of the receptors, receptor for advanced glycation endproducts (RAGEs) and Toll-like receptors (TLRs) 2 and 4.
Related JoVE Video
Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening.
J Am Heart Assoc
PUBLISHED: 11-09-2013
Show Abstract
Hide Abstract
Currently available screening tools for left ventricular (LV) hypertrophy (LVH) and systolic dysfunction (LVSD) are either expensive (echocardiography) or perform suboptimally (B-type natriuretic peptide [BNP]). It is unknown whether newer biomarkers are associated with LVH and LVSD and can serve as screening tools.
Related JoVE Video
A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction.
Eur. Heart J.
PUBLISHED: 09-17-2013
Show Abstract
Hide Abstract
Takotsubo cardiomyopathy (TTC) remains a potentially life-threatening disease, which is clinically indistinguishable from acute myocardial infarction (MI). Today, no established biomarkers are available for the early diagnosis of TTC and differentiation from MI. MicroRNAs (miRNAs/miRs) emerge as promising sensitive and specific biomarkers for cardiovascular disease. Thus, we sought to identify circulating miRNAs suitable for diagnosis of acute TTC and for distinguishing TTC from acute MI.
Related JoVE Video
Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis.
Eur. Heart J.
PUBLISHED: 09-11-2013
Show Abstract
Hide Abstract
The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials.
Related JoVE Video
Risk stratification in critically ill patients: GDF-15 scores in adult respiratory distress syndrome.
Crit Care
PUBLISHED: 07-31-2013
Show Abstract
Hide Abstract
Patients with adult respiratory distress syndrome (ARDS) are highly heterogeneous but current therapies are rather uniform and largely supportive. In the previous issue of Critical Care, Clark and colleagues report that the biomarker GDF-15 provides prognostic information in ARDS that is additive to that provided by the APACHE III score. Patients with high levels of growth-differentiation factor 15 (GDF-15) had a higher mortality and more complicated hospital course. Biomarkers such as GDF-15 may help us to identify patients at higher risk who may eventually benefit from more personalized and targeted therapies.
Related JoVE Video
Biomarkers of cardiovascular stress and incident chronic kidney disease.
Clin. Chem.
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community.
Related JoVE Video
Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation.
Am. Heart J.
PUBLISHED: 07-09-2013
Show Abstract
Hide Abstract
We investigated whether circulating concentrations of soluble ST2, growth differentiation factor-15 (GDF-15), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP).
Related JoVE Video
Incremental prognostic value of biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) score and high-sensitivity cardiac troponin T in non-ST-elevation acute coronary syndrome.
Clin. Chem.
PUBLISHED: 07-01-2013
Show Abstract
Hide Abstract
Guidelines recommend the use of validated risk scores and a high-sensitivity cardiac troponin assay for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). The incremental prognostic value of biomarkers in this context is unknown.
Related JoVE Video
Circulating concentrations of fibroblast activation protein ? in apparently healthy individuals and patients with acute coronary syndrome as assessed by sandwich ELISA.
Int. J. Cardiol.
PUBLISHED: 06-03-2013
Show Abstract
Hide Abstract
Fibroblast activation protein ? (FAP) is a membrane glycoprotein with dipeptidyl-peptidase and collagenase activity and is expressed in cancer, arthritis, and atherosclerotic plaques. We hypothesized that FAP can be measured quantitatively in the circulation and provide prognostic information in acute coronary syndrome (ACS).
Related JoVE Video
Image-guided therapies for myocardial repair: concepts and practical implementation.
Eur Heart J Cardiovasc Imaging
PUBLISHED: 05-29-2013
Show Abstract
Hide Abstract
Cell- and molecule-based therapeutic strategies to support wound healing and regeneration after myocardial infarction (MI) are under development. These emerging therapies aim at sustained preservation of ventricular function by enhancing tissue repair after myocardial ischaemia and reperfusion. Such therapies will benefit from guidance with regard to timing, regional targeting, suitable candidate selection, and effectiveness monitoring. Such guidance is effectively obtained by non-invasive tomographic imaging. Infarct size, tissue characteristics, muscle mass, and chamber geometry can be determined by magnetic resonance imaging and computed tomography. Radionuclide imaging can be used for the tracking of therapeutic agents and for the interrogation of molecular mechanisms such as inflammation, angiogenesis, and extracellular matrix activation. This review article portrays the hypothesis that an integrated approach with an early implementation of structural and molecular tomographic imaging in the development of novel therapies will provide a framework for achieving the goal of improved tissue repair after MI.
Related JoVE Video
Serum hepcidin levels and muscle iron proteins in humans injected with low- or high-dose erythropoietin.
Eur. J. Haematol.
PUBLISHED: 04-05-2013
Show Abstract
Hide Abstract
Inhibition of hepcidin expression by erythropoietic signals is of great physiological importance; however, the inhibitory pathways remain poorly understood. To investigate (i) the direct effect of erythropoietin (Epo) and (ii) the contribution of putative mediators on hepcidin repression, healthy volunteers were injected with a single dose of Epo, either low (63 IU/kg, n = 8) or high (400 IU/kg, n = 6). Low-dose Epo provoked hepcidin down-modulation within 24 h; the effect was not immediate as hepcidin circadian variations were still present following injection. High-dose Epo induced no additional effect on the hepcidin response, that is hepcidin diurnal fluctuations were not abolished in spite of extremely high Epo levels. We did not find significant changes in putative mediators of hepcidin repression, such as transferrin saturation, soluble transferrin receptor, or growth differentiation factor 15. Furthermore, the potential hepcidin inhibitor, soluble hemojuvelin, was found unaltered by Epo stimulation. This finding was consistent with the absence of signs of iron deficiency observed at the level of skeletal muscle tissue. Our data suggest that hepcidin repression by erythropoietic signals in humans may not be controlled directly by Epo, but mediated by a still undefined factor.
Related JoVE Video
Change in growth differentiation factor 15 concentrations over time independently predicts mortality in community-dwelling elderly individuals.
Clin. Chem.
PUBLISHED: 03-25-2013
Show Abstract
Hide Abstract
Growth differentiation factor 15 (GDF-15) is emerging as a powerful risk indicator in both cardiovascular disease patients and community-dwelling individuals. We investigated GDF-15 concentrations and their changes over 5 years in elderly individuals from the community, together with the underlying conditions and prognostic implications of these measurements.
Related JoVE Video
GDF-15 for Prognostication of Cardiovascular and Cancer Morbidity and Mortality in Men.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%, p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%, p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19 to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease morbidity and mortality. The corresponding incremental increase for cancer mortality in the respective total and non-cancer disease (n=882) population was 46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer morbidity and mortality in patients without previous cancer disease 30% (95%CI 12 to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication of both cardiovascular, cancer mortality and morbidity beyond established risk factors and biomarkers of cardiac, renal dysfunction and inflammation.
Related JoVE Video
Highly specific detection of myostatin prodomain by an immunoradiometric sandwich assay in serum of healthy individuals and patients.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Myostatin is a muscle derived factor that functions as a negative regulator of skeletal muscle growth. Induction of myostatin expression was observed in rodent models of muscle wasting and in cachectic patients with cancer or pulmonary disease. Therefore, there is an increasing interest to use serum myostatin as a biomarker.
Related JoVE Video
Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome.
Eur. Heart J.
PUBLISHED: 12-23-2011
Show Abstract
Hide Abstract
The aim of the study was to evaluate whether knowledge of the circulating concentration of growth differentiation factor 15 (GDF-15) adds predictive information to the Global Registry of Acute Coronary Events (GRACE) score, a validated scoring system for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). We also evaluated whether GDF-15 adds predictive information to a model containing the GRACE score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), a prognostic biomarker already in clinical use.
Related JoVE Video
Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-10-2011
Show Abstract
Hide Abstract
Transsignaling of interleukin (IL)-6 is a central pathway in the pathogenesis of disorders associated with chronic inflammation, such as Crohn disease, rheumatoid arthritis, and inflammatory colon cancer. Notably, IL-6 also represents an independent risk factor for coronary artery disease (CAD) in humans and is crucially involved in vascular inflammatory processes.
Related JoVE Video
Relations of growth-differentiation factor-15 to biomarkers reflecting vascular pathologies in a population-based sample of elderly subjects.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 10-24-2011
Show Abstract
Hide Abstract
Growth-differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiac diseases. GDF-15 is commonly related to cardiovascular risk factors, inflammatory activity and cardiac abnormalities. However, it is not clear whether it might be an indicator of vascular pathologies as well.
Related JoVE Video
Leukocyte integrin activation and deactivation: novel mechanisms of balancing inflammation.
J. Mol. Med.
PUBLISHED: 10-05-2011
Show Abstract
Hide Abstract
Leukocyte recruitment into tissue forms the basis of immune surveillance and direct immune defense. It proceeds in a cascade-like fashion. The first contact of leukocytes with the endothelium is mediated by selectins and their counter receptors, followed by rolling and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals which can activate several signaling pathways leading to leukocyte adhesion to the endothelium and transmigration through the blood vessel wall into the inflamed tissue. Whereas inflammatory reactions are beneficial and necessary for host defense, they need to be balanced and controlled to prevent harmful consequences and tissue destruction. In this article, we discuss the different signaling pathways that ensure rapid and efficient integrin activation on leukocytes. In addition, we report on a recently identified novel endogenous mechanism that counteracts and balances integrin activation, thereby limiting leukocyte recruitment and the extent of inflammation. Further investigation of this new mechanism may allow providing new approaches for the development of the next generation of anti-inflammatory drugs.
Related JoVE Video
Clustering of 37 circulating biomarkers by exploratory factor analysis in patients following complicated acute myocardial infarction.
Int. J. Cardiol.
PUBLISHED: 06-12-2011
Show Abstract
Hide Abstract
The objective of this study was to elucidate the complex interactions between families of circulating biomarkers representing different biochemical responses to the pathophysiology following complicated acute myocardial infarction (AMI).
Related JoVE Video
Syndecan-4 signalling inhibits apoptosis and controls NFAT activity during myocardial damage and remodelling.
Cardiovasc. Res.
PUBLISHED: 06-01-2011
Show Abstract
Hide Abstract
Myocardial infarction (MI) results in acute impairment of left ventricular (LV) function through the initial development of cardiomyocyte death and subsequent progression of LV remodelling. The expression of syndecan-4 (Sdc4), a transmembrane proteoglycan, is up-regulated after MI, but its function in the heart remains unknown. Here, we characterize the effects of Sdc4 deficiency in murine myocardial ischaemia and permanent infarction.
Related JoVE Video
Elevated plasma growth differentiation factor-15 correlates with lymph node metastases and poor survival in endometrial cancer.
Clin. Cancer Res.
PUBLISHED: 05-26-2011
Show Abstract
Hide Abstract
The study objective was to investigate and validate plasma growth differentiation factor-15 (GDF-15) as a predictor of lymph node metastasis and a poor prognosis in primary endometrial cancer.
Related JoVE Video
Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome.
J. Mol. Cell. Cardiol.
PUBLISHED: 05-13-2011
Show Abstract
Hide Abstract
Circulating microRNAs may have diagnostic potential in acute coronary syndrome (ACS). Previous studies, however, were based on low patient numbers and could not assess the relation of microRNAs to clinical characteristics and their potential prognostic value. We thus assessed the diagnostic and prognostic value of cardiomyocyte-enriched microRNAs in the context of clinical variables and a sensitive myonecrosis biomarker in a larger ACS cohort. MiR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499 concentrations were measured by quantitative reverse transcription PCR in plasma samples obtained on admission from 444 patients with ACS. High-sensitivity troponin T (hsTnT) was measured by immunoassay. Patients were followed for 6 months regarding all-cause mortality. In a multiple linear regression analysis that included clinical variables and hsTnT, miR-1, miR-133a, miR-133b, and miR-208b were independently associated with hsTnT levels (all P<0.001). Patients with myocardial infarction presented with higher levels of miR-1, miR-133a, and miR-208b compared with patients with unstable angina. However, all six investigated microRNAs showed a large overlap between patients with unstable angina or myocardial infarction. MiR-133a and miR-208b levels were significantly associated with the risk of death in univariate and age- and gender-adjusted analyses. Both microRNAs lost their independent association with outcome upon further adjustment for hsTnT. The present study tempers speculations about the potential usefulness of cardiomyocyte-enriched microRNAs as diagnostic or prognostic markers in ACS.
Related JoVE Video
Growth differentiation factor 15 plasma levels and outcome after ischemic stroke.
Cerebrovasc. Dis.
PUBLISHED: 03-28-2011
Show Abstract
Hide Abstract
Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that is induced after experimental brain injury. We hypothesized that the circulating levels of GDF-15 are increased and associated with neurological outcome in patients with ischemic stroke.
Related JoVE Video
Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors.
J. Clin. Invest.
PUBLISHED: 02-05-2011
Show Abstract
Hide Abstract
Tissue homeostasis and remodeling are processes that involve high turnover of biological macromolecules. Many of the waste molecules that are by-products or degradation intermediates of biological macromolecule turnover enter the circulation and are subsequently cleared by liver sinusoidal endothelial cells (LSEC). Besides the mannose receptor, stabilin-1 and stabilin-2 are the major scavenger receptors expressed by LSEC. To more clearly elucidate the functions of stabilin-1 and -2, we have generated mice lacking stabilin-1, stabilin-2, or both stabilin-1 and -2 (Stab1–/– Stab2–/– mice). Mice lacking either stabilin-1 or stabilin-2 were phenotypically normal; however, Stab1–/– Stab2–/– mice exhibited premature mortality and developed severe glomerular fibrosis, while the liver showed only mild perisinusoidal fibrosis without dysfunction. Upon kidney transplantation into WT mice, progression of glomerular fibrosis was halted, indicating the presence of profibrotic factors in the circulation of Stab1–/– Stab2–/– mice. While plasma levels of known profibrotic cytokines were unaltered, clearance of the TGF-? family member growth differentiation factor 15 (GDF-15) was markedly impaired in Stab1–/– Stab2–/– mice but not in either Stab1–/– or Stab2–/– mice, indicating that it is a common ligand of both stabilin-1 and stabilin-2. These data lead us to conclude that stabilin-1 and -2 together guarantee proper hepatic clearance of potentially noxious agents in the blood and maintain tissue homeostasis not only in the liver but also distant organs.
Related JoVE Video
GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice.
Nat. Med.
PUBLISHED: 02-01-2011
Show Abstract
Hide Abstract
Inflammatory cell recruitment after myocardial infarction needs to be tightly controlled to permit infarct healing while avoiding fatal complications such as cardiac rupture. Growth differentiation factor-15 (GDF-15), a transforming growth factor-? (TGF-?)-related cytokine, is induced in the infarcted heart of mice and humans. We show that coronary artery ligation in Gdf15-deficient mice led to enhanced recruitment of polymorphonuclear leukocytes (PMNs) into the infarcted myocardium and an increased incidence of cardiac rupture. Conversely, infusion of recombinant GDF-15 repressed PMN recruitment after myocardial infarction. In vitro, GDF-15 inhibited PMN adhesion, arrest under flow and transendothelial migration. Mechanistically, GDF-15 counteracted chemokine-triggered conformational activation and clustering of ?(2) integrins on PMNs by activating the small GTPase Cdc42 and inhibiting activation of the small GTPase Rap1. Intravital microscopy in vivo in Gdf15-deficient mice showed that Gdf-15 is required to prevent excessive chemokine-activated leukocyte arrest on the endothelium. Genetic ablation of ?(2) integrins in myeloid cells rescued the mortality of Gdf15-deficient mice after myocardial infarction. To our knowledge, GDF-15 is the first cytokine identified as an inhibitor of PMN recruitment by direct interference with chemokine signaling and integrin activation. Loss of this anti-inflammatory mechanism leads to fatal cardiac rupture after myocardial infarction.
Related JoVE Video
Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction.
Circulation
PUBLISHED: 01-24-2011
Show Abstract
Hide Abstract
Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart.
Related JoVE Video
GATA6 promotes angiogenic function and survival in endothelial cells by suppression of autocrine transforming growth factor beta/activin receptor-like kinase 5 signaling.
J. Biol. Chem.
PUBLISHED: 12-02-2010
Show Abstract
Hide Abstract
Understanding the transcriptional regulation of angiogenesis could lead to the identification of novel therapeutic targets. We showed here that the transcription factor GATA6 is expressed in different human primary endothelial cells as well as in vascular endothelial cells of mice in vivo. Activation of endothelial cells was associated with GATA6 nuclear translocation, chromatin binding, and enhanced GATA6-dependent transcriptional activation. siRNA-mediated down-regulation of GATA6 after growth factor stimulation led to a dramatically reduced capacity of macro- and microvascular endothelial cells to proliferate, migrate, or form capillary-like structures on Matrigel. Adenoviral overexpression of GATA6 in turn enhanced angiogenic function, especially in cardiac endothelial microvascular cells. Furthermore, GATA6 protected endothelial cells from undergoing apoptosis during growth factor deprivation. Mechanistically, down-regulation of GATA6 in endothelial cells led to increased expression of transforming growth factor (TGF) ?1 and TGF?2, whereas enhanced GATA6 expression, accordingly, suppressed Tgfb1 promoter activity. High TGF?1/?2 expression in GATA6-depleted endothelial cells increased the activation of the activin receptor-like kinase 5 (ALK5) and SMAD2, and suppression of this signaling axis by TGF? neutralizing antibody or ALK5 inhibition restored angiogenic function and survival in endothelial cells with reduced GATA6 expression. Together, these findings indicate that GATA6 plays a crucial role for endothelial cell function and survival, at least in part, by suppressing autocrine TGF? expression and ALK5-dependent signaling.
Related JoVE Video
Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-21-2010
Show Abstract
Hide Abstract
To investigate growth differentiation factor (GDF)-15 at hospital discharge for assessment of the risk of death, recurrent myocardial infarction (MI), and congestive heart failure, and to determination of whether these risks can be modified by statins.
Related JoVE Video
Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial.
Circulation
PUBLISHED: 09-20-2010
Show Abstract
Hide Abstract
Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic biomarker in patients with coronary artery disease. Little is known about GDF-15 as a biomarker in patients with heart failure.
Related JoVE Video
Multiple marker approach to risk stratification in patients with stable coronary artery disease.
Eur. Heart J.
PUBLISHED: 09-18-2010
Show Abstract
Hide Abstract
multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina.
Related JoVE Video
Effective blockage of both the extrinsic and intrinsic pathways of apoptosis in mice by TAT-crmA.
J. Biol. Chem.
PUBLISHED: 04-28-2010
Show Abstract
Hide Abstract
Evidence accumulates that in clinically relevant cell death, both the intrinsic and extrinsic apoptotic pathway synergistically contribute to organ failure. In search for an inhibitor of apoptosis that provides effective blockage of these pathways, we analyzed viral proteins that evolved to protect the infected host cells. In particular, the cowpox virus protein crmA has been demonstrated to be capable of blocking key caspases of both pro-apoptotic pathways. To deliver crmA into eukaryotic cells, we fused the TAT protein transduction domain of HIV to the N terminus of crmA. In vitro, the TAT-crmA fusion protein was efficiently translocated into target cells and inhibited apoptosis mediated through caspase-8, caspase-9, and caspase-3 after stimulation with alpha-Fas, etoposide, doxorubicin, or staurosporine. The extrinsic apoptotic pathway was investigated following alpha-Fas stimulation. In vivo 90% of TAT-crmA-treated animals survived an otherwise lethal dose of alpha-Fas and showed protection from Fas-induced organ failure. To examine the intrinsic apoptotic pathway, we investigated the survival of mice treated with an otherwise lethal dose of doxorubicin. Whereas all control mice died within 31 days, 40% of mice that concomitantly received intraperitoneal injections of TAT-crmA survived. To test the ability to comprehensively block both the intrinsic and extrinsic apoptotic pathway in a clinically relevant setting, we employed a murine cardiac ischemia-reperfusion model. TAT-crmA reduced infarction size by 40% and preserved left ventricular function. In summary, these results provide a proof of principle for the inhibition of apoptosis with TAT-crmA, which might provide a new treatment option for ischemia-reperfusion injuries.
Related JoVE Video
Growth differentiation factor-15 as a prognostic biomarker in ovarian cancer.
Gynecol. Oncol.
PUBLISHED: 04-27-2010
Show Abstract
Hide Abstract
There is a need for identification of new biomarkers improving our understanding, diagnosis, and follow-up of ovarian cancer. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta superfamily, and GDF-15 overexpression has been found in several cancer forms but has not been explored in ovarian cancer. The aim of the study was to explore preoperative plasma concentration and tissue expression of growth differentiation factor (GDF)-15 in ovarian tumors.
Related JoVE Video
Cell therapy for the treatment of coronary heart disease: a critical appraisal.
Nat Rev Cardiol
PUBLISHED: 02-23-2010
Show Abstract
Hide Abstract
Randomized, controlled clinical trials have demonstrated that cell therapy can improve the recovery of cardiac function in patients after acute myocardial infarction (AMI). Trial results are inconsistent, however, and uncertainty persists regarding the mechanism of action and prospect of cell therapy for patients with heart disease. This Review examines the results from the first-generation trials and discusses procedure-related variables that could have determined treatment outcomes. Obvious issues, including optimal timing of cell transfer, dose, and delivery methods are being investigated in ongoing second-generation trials. These studies aim to refine the protocols and identify the patients who will benefit most from cell therapy. Third-generation trials will address the current limitations of cell therapy, such as cell retention and cell survival after transplantation, and impaired cell functionality in patients with advanced cardiovascular disease. The secretion of factors with paracrine effects by the transplanted cells is an increasingly recognized phenomenon. Identification of these factors, by secretome analyses and bioinformatic approaches, could advance protein-based therapies to promote healing and inhibit pathological remodeling of the heart after AMI. The identification of reliable sources of pluripotent stem cells and their differentiation into mature cardiac cell types could ultimately enable regeneration of the infarcted heart.
Related JoVE Video
Improving long-term risk prediction in patients with acute chest pain: the Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers.
Am. Heart J.
PUBLISHED: 01-16-2010
Show Abstract
Hide Abstract
The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome. However, there is limited knowledge regarding the utility of this score for long-term risk prediction in unselected patients with acute chest pain and whether it might be improved by the integration of nonnecrosis biomarkers.
Related JoVE Video
Growth differentiation factor-15: a new biomarker in cardiovascular disease.
Herz
PUBLISHED: 12-22-2009
Show Abstract
Hide Abstract
Growth differentiation factor-(GDF-)15 is a stress-responsive cytokine that is emerging as a biomarker of cardiac and vascular dysfunction and disease. Elevated circulating levels of GDF-15 identify high-risk individuals across the cardiovascular continuum, from stable coronary artery disease to acute coronary syndrome and heart failure. The association of GDF-15 with outcome in these conditions is independent of clinical risk factors and established biomarkers, including NT-proBNP (N-terminal pro-B-type natriuretic peptide) and troponin. The prognostic information provided by GDF-15 in cardiovascular disease may inform patient management, e.g., by identifying patients with non-ST segment elevation acute coronary syndrome who benefit from an invasive strategy, or by monitoring treatment response in heart failure. Future studies need to evaluate prospectively whether GDF-15, alone or as part of a multimarker strategy, can improve contemporary risk prediction algorithms and support therapeutic management of patients with cardiovascular disease.
Related JoVE Video
Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome.
Circ Cardiovasc Genet
PUBLISHED: 12-11-2009
Show Abstract
Hide Abstract
Growth-differentiation factor-15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome. This study assessed the time course and the long-term prognostic relevance of GDF-15 levels measured repetitively in patients with non-ST-segment-elevation acute coronary syndrome during 6 months after the acute event.
Related JoVE Video
Long-term effects of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: 5-year results from the randomized-controlled BOOST trial--an echocardiographic study.
Eur J Echocardiogr
PUBLISHED: 11-28-2009
Show Abstract
Hide Abstract
We have recently observed that intracoronary autologous bone marrow cell (BMC)-transfer improves parameters of diastolic function in patients after acute myocardial infarction at 6 and 18 months. There is no clinical study addressing the long-term effect of BMC transfer on diastolic function. Therefore, we conducted a 5-year follow-up of the BOOST trial to evaluate a sustained benefit on echocardiographic parameters on diastolic function.
Related JoVE Video
Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial.
Eur. Heart J.
PUBLISHED: 09-22-2009
Show Abstract
Hide Abstract
We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27).
Related JoVE Video
Calcineurin protects the heart in a murine model of dilated cardiomyopathy.
J. Mol. Cell. Cardiol.
PUBLISHED: 09-01-2009
Show Abstract
Hide Abstract
Dilated cardiomyopathy (DCM) is a relatively common disease with a poor prognosis. Given that the only meaningful treatment for DCM is cardiac transplantation, investigators have explored the underlying molecular mechanisms of this disease in the hopes of identifying novel therapeutic targets. One such target is the serine-threonine phosphatase calcineurin, a Ca2+-activated signaling factor that is known to regulate the cardiac hypertrophic program, although its role in DCM is currently unknown. In order to address this issue, we crossed muscle lim protein (MLP) knock-out mice-a murine model of DCM-with calcineurin A beta ko mice, which lack the stress responsive isoform of calcineurin that critically regulates the cardiac hypertrophic response. Interestingly, the majority (73%) of the MLP/calcineurin A beta double knock-out mice died within 20 days of birth with signs of cardiomyopathy. Ultrastructural examination revealed enhanced cardiomyocyte apoptosis and necrosis in the postnatal myocardium of these mice. The MLP/calcineurin A beta double knock-out mice that survived until adulthood showed reduced left ventricular function, enhanced apoptotic and necrotic cardiomyocyte death and augmented myocardial fibrosis compared to various control groups. Antithetically, mild overexpression of activated calcineurin in the mouse heart improved function and adverse remodeling in MLP knock-out mice. Collectively, these results reveal an important and previously unrecognized protective function of endogenous myocardial calcineurin in a mouse model of dilated cardiomyopathy.
Related JoVE Video
Growth-differentiation factor-15 in heart failure.
Heart Fail Clin
PUBLISHED: 07-28-2009
Show Abstract
Hide Abstract
The stress-responsive transforming growth factor-beta-related cytokine, growth-differentiation factor-15 (GDF-15), is emerging as a new biomarker in patients with cardiovascular disease. The circulating levels of GDF-15 are elevated and independently related to an adverse prognosis in acute coronary syndrome and left- or right-sided heart failure. GDF-15 adds significant prognostic information to established clinical and biochemical risk markers in these conditions. Elevated levels of GDF-15 may identify patients who have non-ST-elevation acute coronary syndrome who derive the greatest benefit from an invasive treatment strategy. As with other heart failure biomarkers, including BNP, it is currently not known what specific therapies could be used to reduce the risk associated with elevated levels of GDF-15 in heart failure. Further elucidation of the pathobiology and upstream inducers of this new biomarker may lead to new therapeutic concepts that address the risk associated with elevated GDF-15 levels. A commercial assay for GDF-15 should be available in the near future.
Related JoVE Video
Circulating concentrations of follistatin-like 1 in healthy individuals and patients with acute coronary syndrome as assessed by an immunoluminometric sandwich assay.
Clin. Chem.
PUBLISHED: 07-02-2009
Show Abstract
Hide Abstract
Follistatin-like 1 (FSTL1) is a 308-amino acid secreted glycoprotein. Tissue levels of FSTL1 are induced in animal models and patients with chronic inflammatory and cardiovascular disease. We hypothesized that FSTL1 can be measured in the human circulation and used as a biomarker in acute coronary syndrome (ACS).
Related JoVE Video
A network against failing hearts--introducing the German "Competence Network Heart Failure".
Int. J. Cardiol.
PUBLISHED: 06-26-2009
Show Abstract
Hide Abstract
Heart failure (HF) has been identified as one of the most threatening diseases for the western civilisation, posing a risk to health for a rising number of patients. Acknowledging the medical problem of HF to be both economically and socially threatening the German Federal Ministry of Research and Education (BMBF) initiated a nationwide research network aiming to find new ways in prevention, alleviation and treatment of the widespread disease. The "Competence Network Heart Failure" (CNHF), initiated in 2003, bundles the scientific expertise in a large-scale research network; its aims are the coordination of basic and applied clinical research as well as dissemination of findings into clinical practice in order to consolidate and perpetuate the achieved improvements. The scope of this paper is to introduce the CNHF and to provide an overview of the tasks and hitherto attained achievements to a broad spectrum of health care providers.
Related JoVE Video
Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study.
Eur. Heart J.
PUBLISHED: 06-26-2009
Show Abstract
Hide Abstract
Growth-differentiation factor-15 (GDF-15) is emerging as an independent prognostic biomarker in patients with cardiovascular (CV) disease. Little is known about the pathophysiological basis for the close association of GDF-15 to future CV events. We hypothesized that GDF-15 is related to underlying CV pathologies.
Related JoVE Video
Circulating and placental growth-differentiation factor 15 in preeclampsia and in pregnancy complicated by diabetes mellitus.
Hypertension
PUBLISHED: 05-26-2009
Show Abstract
Hide Abstract
Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming growth factor-beta-related cytokine, is emerging as a new risk marker in patients with cardiovascular disease. We explored GDF-15 in preeclampsia and in diabetic pregnancies, because these conditions are associated with augmented risk for cardiovascular disease, both in mother and in offspring. Plasma from pregnant women (n=267; controls: n=59, preeclampsia: n=85, diabetes mellitus: n=112, and superimposed preeclampsia in diabetes mellitus: n=11), fetal plasma (n=72), and amniotic fluid (n=99) were analyzed by immunoassay for GDF-15. Placental GDF-15 mRNA and protein expression levels were analyzed by quantitative real-time PCR and immunoblots in 78 and 18 pregnancies, respectively. Conditioned media from preeclamptic (n=6) and control (n=6) villous placenta explants were analyzed by immunoassay for GDF-15. Median maternal GDF-15 concentration was elevated in those with diabetes mellitus, as compared with controls (91 549 versus 79 875 ng/L; P=0.02). Median GDF-15 concentration was higher in patients with preeclampsia than in controls in term maternal blood samples (127 061 versus 80 319 ng/L; P<0.001). In the fetal circulation and amniotic fluid, GDF-15 was elevated in preeclampsia and superimposed preeclampsia in diabetes mellitus, as compared with controls. GDF-15 placental mRNA expression was elevated in preeclampsia, as compared with controls (P=0.002). Placenta immunoblots confirmed a single GDF-15 protein band, and a time-dependent increase in GDF-15 protein was detected in the conditioned media. Our study is the first to show that GDF-15 is dysregulated, both in preeclampsia and in diabetic pregnancies. The mechanisms and diagnostic implications of these findings remain to be explored.
Related JoVE Video
Lidocaine protects from myocardial damage due to ischemia and reperfusion in mice by its antiapoptotic effects.
Anesthesiology
PUBLISHED: 04-09-2009
Show Abstract
Hide Abstract
Perioperative myocardial ischemia poses a vital threat to surgical patients. Means to protect postischemic myocardium are clinically not available. Lidocaine has been demonstrated to exert antiinflammatory pleiotropic effects. The authors set out to test if lidocaine protects ischemic myocardium from reperfusion injury.
Related JoVE Video
Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study.
Circ Cardiovasc Genet
PUBLISHED: 03-31-2009
Show Abstract
Hide Abstract
Growth-differentiation factor-15 (GDF-15) is a stress-responsive transforming growth factor-beta-related cytokine that has emerged as a prognostic biomarker in acute coronary syndrome trial populations. Its predictive role in stable coronary heart disease (CHD) has never been assessed.
Related JoVE Video
Potential novel pharmacological therapies for myocardial remodelling.
Cardiovasc. Res.
PUBLISHED: 03-27-2009
Show Abstract
Hide Abstract
Left ventricular (LV) remodelling remains an important treatment target in patients after myocardial infarction (MI) and chronic heart failure (CHF). Accumulating evidence has supported the concept that beneficial effects of current pharmacological treatment strategies to improve the prognosis in these patients, such as angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 receptor blocker therapy, and beta-blocker therapy, are related, at least in part, to their effects on LV remodelling and dysfunction. However, despite modern reperfusion therapy after MI and optimized treatment of patients with CHF, LV remodelling is observed in a substantial proportion of patients and is associated with an adverse clinical outcome. These observations call for novel therapeutic strategies to prevent or even reverse cardiac remodelling. Recent insights from experimental studies have provided new targets for interventions to prevent or reverse LV remodelling, i.e. reduced endothelial nitric oxide (NO) synthase-derived NO availability, activation of cardiac and leukocyte-dependent oxidant stress pathways, inflammatory pathway activation, matrix-metalloproteinase activation, or stem cell transfer and delivery of novel paracrine factors. An important challenge in translating these observations from preclinical studies into clinical treatment strategies relates to the fact that clinical studies are designed on top of established pharmacological therapy, whereas most experimental studies have tested novel interventions without concomitant drug regimens such as ACE inhibitors or beta-blockers. Therefore, animal studies may overestimate the effect of potential novel treatment strategies on LV remodelling and dysfunction, since established pharmacological therapies may act, in part, via identical or similar signalling pathways. Nevertheless, preclinical studies provide essential information for identifying potential novel targets, and their potential drawbacks, and are required for developing novel clinical treatment strategies to prevent or reverse LV remodelling and dysfunction.
Related JoVE Video
Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin.
Blood
PUBLISHED: 03-04-2009
Show Abstract
Hide Abstract
The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.
Related JoVE Video
Clinical and genetic correlates of growth differentiation factor 15 in the community.
Clin. Chem.
Show Abstract
Hide Abstract
Growth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively.
Related JoVE Video
Growth differentiation factor 15 in heart failure: an update.
Curr Heart Fail Rep
Show Abstract
Hide Abstract
Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine expressed in the cardiovascular system. GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. GDF-15 integrates information from cardiac and extracardiac disease pathways that are linked to the incidence, progression, and prognosis of heart failure (HF). Increased circulating levels of GDF-15 are associated with an increased risk of developing HF in apparently healthy individuals from the community. After an acute coronary syndrome, elevated levels of GDF-15 are indicative of an increased risk of developing adverse left ventricular remodeling and HF. In?patients with established HF, the levels of GDF-15 and increases in GDF-15 over time are associated with adverse outcomes. The information provided by GDF-15 is independent of established risk factors and cardiac biomarkers, including BNP. More studies are needed to elucidate how the information provided by GDF-15 can be?used for patient monitoring and formulating treatment decisions. Further understanding of the pathobiology of GDF-15 may lead to the discovery of new treatment targets in HF.
Related JoVE Video
Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial.
Eur. J. Endocrinol.
Show Abstract
Hide Abstract
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals.
Related JoVE Video
Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.
Circulation
Show Abstract
Hide Abstract
Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity.
Related JoVE Video
Identification of follistatin-like 1 by expression cloning as an activator of the growth differentiation factor 15 gene and a prognostic biomarker in acute coronary syndrome.
Clin. Chem.
Show Abstract
Hide Abstract
Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers.
Related JoVE Video
Anti-inflammatory mechanisms and therapeutic opportunities in myocardial infarct healing.
J. Mol. Med.
Show Abstract
Hide Abstract
The wound healing response after myocardial infarction (MI) involves a cascade of molecular and cellular events that lead to a replacement of the necrotic area with a collagen-rich scar. Clearance of necrotic debris by neutrophils, monocytes, and macrophages is a critical component of infarct healing; however, tight control and timely repression of this inflammatory response is important to prevent excessive tissue degradation leading to infarct expansion and heart failure. Genetic ablation or blockade of anti-inflammatory pathways tends to be detrimental after MI, whereas genetic ablation of pro-inflammatory pathways tends to be beneficial. Accordingly, therapies enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways have been found to improve wound healing and to reduce the risk of heart failure in rodent models of acute MI. Besides their scavenger function, inflammatory cells promote healing by stimulating angiogenesis and granulation tissue formation via paracrine factors. Moreover, signaling mediators that are active in inflammatory cells may be active also in non-inflammatory cell types involved in infarct healing. Some anti-inflammatory interventions are therefore deleterious. However, interventions that carefully adjust the balance between the essential and detrimental facets of inflammation may provide new therapeutic opportunities for patients with large MIs who continue to be at risk of developing heart failure, despite modern reperfusion and anti-remodeling strategies.
Related JoVE Video

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.

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.