Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease

• Published in: Current Issues in Molecular Biology Vol. 45; no. 8; pp. 6823 - 6841
• Main Authors: Dergunov, Alexander D, Nosova, Elena V, Rozhkova, Alexandra V, Vinogradina, Margarita A, Baserova, Veronika B, Popov, Mikhail A, Limborska, Svetlana A, Dergunova, Liudmila V
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.08.2023; MDPI
• Subjects: Apolipoproteins; Atherosclerosis; Cholesterol; coronary artery disease; Coronary heart disease; differentially expressed genes; Gene expression; Genes; Genetic aspects; HDL metabolism; Inflammation; Medical research; Medicine, Experimental; Physiological aspects
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb45080431

Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 genes) and atherosclerosis-prone (41 genes) in RNA isolated from peripheral blood mononuclear cells was measured by real-time RT-PCR. Twenty-eight DEGs were identified. The expression of cholesterol transporters, ALB, APOA1, and LCAT was down-regulated, while the expression of AMN, APOE, LDLR, LPL, PLTP, PRKACA, and CETP was up-regulated. The systemic inflammation in CAD is evidenced by the up-regulation of IL1B, TLR8, CXCL5, and TNFRSF1A. For the controls, TLR8 and SOAT1 were negative predictors of the HDL-C level. For CAD patients, PRKACG, PRKCQ, and SREBF1 were positive predictors, while PRKACB, LCAT, and S100A8 were negative predictors. For CAD patients, the efficiency of reverse cholesterol transport is 73–79%, and intracellular free cholesterol seems to accumulate at hyperalphalipoproteinemia. Both atheroprotective (via S100A8) and proatherogenic (via SREBF1, LCAT, PRKACG, PRKACB, and PRKCQ) associations of gene expression with HDL-C determine HDL functionality in CAD patients. The selected key genes and involved pathways may represent HDL-specific targets for the diagnosis and treatment of CAD and atherosclerosis.