Identification of new genes differentially expressed in coronary artery disease by expression profiling.
Genetic factors increase the risk to coronary artery disease (CAD). To date, a limited number of genes that potentially contribute to development of CAD have been identified. In this study, we have performed large-scale gene expression analysis of approximately 12,000 human genes in nine severely atherosclerotic and six nonatherosclerotic human coronary arteries using oligonucleotide microarrays. Fifty-six genes showed differential expression in atherosclerotic coronary artery tissues; expression of 55 genes was increased in atherosclerotic coronary arteries, whereas only one gene, GST, encoding a reducing agent, showed downregulated expression. The expression data of selected genes were validated by quantitative RT-PCR analysis as well as immunostaining. The associations of 49 genes with CAD appear to be novel, and they include genes encoding ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, beta2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-alpha-induced protein 2 (B94), and flavocytochrome 558. In conclusion, we have identified 56 genes whose expression is associated with CAD, and 49 of them may represent new genes linked to CAD.
Archacki
Stephen R
SR
Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland 44115, USA.
Angheloiu
George
G
Tian
Xiao-Li
XL
Tan
Fen Lai
FL
DiPaola
Nick
N
Shen
Gong-Qing
GQ
Moravec
Christine
C
Ellis
Stephen
S
Topol
Eric J
EJ
Wang
Qing
Q
D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D003331:Coronary Vessels; D005109:Extracellular Matrix / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D050356:Lipid Metabolism; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction