Year: 2011
Type: article
Abstract: Despite the identification of the risk factors which lead to CAD, we hypothesize there are novel genes to be identified that cause dysfunctional mechanisms leading to disease.For these discoveries, we utilized the genechip also referred to as a microarray.We did expression profiling of coronary arteries from human patients with and without disease and identified 56 genes.The association of 49 genes with CAD appears to be novel, and they included genes: ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, ß2arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-α-induced protein 2 (B94), and flavocytochrome 558.It is well-known that IMAs are resistant to the development of atherosclerosis, whereas the coronary arteries are athero-prone.The contrasting properties of these arteries provides an innovative strategy to identify the gene(s) that may play important roles in the development of CAD.We found 29 genes with a significant difference in their expression levels between IMA and the coronary artery which included the TES gene encoding Testin.Using assays relevant to atherosclerosis, we showed that the knockdown of TES expression by siRNA promoted oxLDL-mediated monocyte adhesion to endothelial cells (EC), EC migration, and the transendothelial migration of monocytes, while the overexpression of TES in ECs blunted these processes.These results define a new molecular determinant (TES) for CAD and establish a novel role for TES.We also investigated the gene expression of the ECs harvested from IMA and Cor to further distinguish these arteries' differential sensitivities to the develop atherosclerosis.The most statistically significant gene identified was the adenosine A2B receptor (A2B).Consequently, A2B was selected for follow-up functional studies to define its role(s) in ECs and how it may promote a resistance to atherosclerosis.We showed that the over-expression of the A2B receptor blunted processes relevant to the atherosclerosis.In sum, expression profiling offered us the opportunity to identify novel genes that may be related to atherosclerosis.The identification of genes associated with this disease may lead to more aggressive interventions to halt the disease process of atherosclerosis by understanding the underlying genetic processes.vi
Author: Stephen Archacki
Institution: Cleveland State University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2336074835