Project description:Peripheral blood RNA-Seq from human coronary artery calcification cases and controls; Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques.
Project description:Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary and iliac artery ECs. We demonstrate that in vivo the endothelial transcriptional profile of a coronary artery (the right coronary artery) is intrinsically different from that of a major conduit vessel (the external iliac artery), and that this difference is consistent with former vessel being more prone to atherosclerosis. Keywords: coronary atherosclerosis, endothelial heterogeneity, microarray, gene expression Endothelial cells were freshly harvest from right coronary, left and right iliac arteries from four pigs. RNA were isolated and expression profiles were obtained using olig microarrays.
Project description:Phenotypic heterogeneity among arterial ECs is particularly relevant to atherosclerosis since the disease occurs predominantly in major arteries, which vary in their atherosusceptibility. To explore EC heterogeneity, we used DNA microarrays to compare gene expression profiles of freshly harvested porcine coronary and iliac artery ECs. We demonstrate that in vivo the endothelial transcriptional profile of a coronary artery (the right coronary artery) is intrinsically different from that of a major conduit vessel (the external iliac artery), and that this difference is consistent with former vessel being more prone to atherosclerosis. Keywords: coronary atherosclerosis, endothelial heterogeneity, microarray, gene expression
Project description:Currently, it is well established that human endothelial cells (ECs) are characterised by a significant heterogeneity between distinct blood vessels, e.g., arteries, veins, capillaries, and lymphatic vessels. Further, even ECs belonging to the same lineage but grown under different flow patterns (e.g., laminar and oscillatory or turbulent flow) ostensibly have distinct molecular profiles defining their physiological behaviour. Human coronary artery endothelial cells (HCAEC) and human internal thoracic artery endothelial cells (HITAEC) represent two cell lines inhabiting atheroprone and atheroresistant blood vessels (coronary artery and internal thoracic artery, respectively). Resistance of the internal mammary artery to atherosclerosis has been largely attributed to the protective phenotype of HITAEC which reportedly produce higher amounts of vasodilators including nitric oxide (NO) through the respective signaling pathways. However, this hypothesis has not been adequately addressed hitherto as proteomic profiling of HCAEC and HITAEC in a head-to-head comparison setting has not been performed.
Project description:Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotype information to identify quantitative trait loci (QTL) for gene expression and splicing in coronary arteries obtained from 138 ancestrally diverse Americans.
Project description:To investigate the expression profiles of miRNA in atherosclerotic plaques, the global features of miRNAs expression of three normal coronary artery tissues sample pools and three sample pools of advanced atherosclerosis plaques of coronary artery were studied using microarray technology,
Project description:Vascular endothelial cells play an important role in the development of coronary artery disease, their injury leads to coronary heart disease and atherosclerosis. This study aimed to elucidate the role of FOXO3-regulated target gene expression and alternative splicing in vascular endothelial cell injury in coronary artery disease
Project description:Innate immune cells importantly contribute to the pathphysiology of atherosclerotic cardiovascular disease CVD. Previous studies show that isolated innate immune cells from patients with atherosclerotic CVD have an activated phenotype. To understand the origin of this immune cell activation, we performed bone marrow aspiration in 10 male patients with severe coronary artery disease (based on coronary CT angiography) and 10 control subjects in whom coronary atherosclerosis was excluded. After flow sorting of HSCs, MPPs, and GMPs, we performed RNAseq.
Project description:Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin sensitive control but the mechanisms that mediate the atherosclerosis phenotype are unknown. The objective of this study is to investigate whether the severity of atherosclerosis is associated not only with lipoprotein concentrations, weight, blood pressure, biomarkers of inflammation and IR in an animal model but also changes in parameters that measure protein glycation. The experimental approach was to study normocholestrolemic pigs fed a high fat diet that also contained increased NaCl. The choice of pigs was driven by the fact that, like humans, they develop coronary artery and aortic atherosclerosis and insulin resistance. In addition, pigs have been used in many studies to define the mechanisms that mediate increased atherosclerosis in diabetes.