Expression of Preselected Genes in Mononuclear Blood Cells Is Associated With the Extent of Coronary Artery Stenosis

The expression levels of genes involved in high-density lipoprotein metabolism and atherogenesis and underlying metabolic pathways were aimed to relate to the number of stenotic coronary arteries. The expression of 65 preselected genes in the peripheral blood mononuclear cells of control patients (n = 63) and coronary artery disease (CAD) patients with one or two (low stenosis group, n = 35) or three or four (high stenosis group, n = 41) stenotic vessels, confirmed by coronary angiography, was measured with real-time PCR. Functional enrichment analysis was applied for annotation of differentially expressed genes. Differentially expressed genes in CAD patients compared to controls were characterized by metabolic pathways connected to plasma lipoprotein assembly, remodeling, and clearance and signaling and regulation of gene expression linked to cholesterol transport and efflux. However, specific expression profiles and metabolic pathways existed for high versus low stenosis comparisons. The expression of the CETP, PLTP, CD36, IL18, ITGB3, S100A8, S100A12, and VEGFA genes increased with the increase in the number of stenotic vessels, which suggests the involvement of these genes in stenosis expansion via lipoprotein metabolism, inflammation, angiogenesis, and innate immunity. The ITGB3, VEGFA, and CETP hub genes were selected as new signature of the expansion of coronary artery stenosis, which was validated with the GSE12288 dataset, with a combined OR value of 7.49 (95% CI, 2.21 to 25.43). The expression levels of the ITGB3, VEGFA, and CETP genes may be used for the diagnosis, prognosis estimation, and treatment of coronary stenosis with strong predictive power.