HDL Cholesterol-Associated Shifts in the Expression of Preselected Genes Reveal both Pro-Atherogenic and Atheroprotective Effects of HDL in Coronary Artery Disease.

Autor:	Dergunov AD; Laboratory of Structural Fundamentals of Lipoprotein Metabolism, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia., Nosova EV; Laboratory of Human Molecular Genetics, National Research Center 'Kurchatov Institute', 123182 Moscow, Russia., Rozhkova AV; Laboratory of Human Molecular Genetics, National Research Center 'Kurchatov Institute', 123182 Moscow, Russia., Vinogradina MA; Laboratory of Human Molecular Genetics, National Research Center 'Kurchatov Institute', 123182 Moscow, Russia., Baserova VB; Laboratory of Structural Fundamentals of Lipoprotein Metabolism, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia., Popov MA; Cardiosurgery Department, M.F. Vladimirsky Moscow Regional Research and Clinical Institute MONIKI, 129090 Moscow, Russia., Limborska SA; Laboratory of Human Molecular Genetics, National Research Center 'Kurchatov Institute', 123182 Moscow, Russia., Dergunova LV; Laboratory of Human Molecular Genetics, National Research Center 'Kurchatov Institute', 123182 Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in bioscience (Landmark edition) [Front Biosci (Landmark Ed)] 2024 Nov 21; Vol. 29 (11), pp. 396.
DOI:	10.31083/j.fbl2911396
Abstrakt:	Background: The associations of high-density lipoprotein (HDL) level and functionality with lipid metabolism, inflammation, and innate immunity in coronary artery disease (CAD) remain controversial. The differential expression of a set of genes related to HDL metabolism (24 genes) and atherogenesis (41 genes) in peripheral blood mononuclear cells (PBMC) from CAD and control patients with varied HDL cholesterol (HDL-C) levels was compared. Methods: 76 male patients 40-60 years old with CAD diagnosed by angiography and 63 control patients were divided into three groups with low, normal (1.0-1.4 mM), and increased HDL-C levels. Transcript levels were measured by real-time PCR. The differentially expressed genes (DEGs) and associated metabolic pathways were analyzed for three groups, with prevalent CAD as an outcome. Results: The common feature was the increased odds ratio values for liver X receptor (LXR) gene expression for three patient groups. CAD patients with low HDL-C possessed 24 DEGs with lower expression of genes involved in cholesterol efflux, and down-regulated SREBF1 and ABCG1 are suggested as gene signatures. CAD patients with normal HDL-C possessed nine DEGs with down-regulated ITGAM and ALB as gene signatures. CAD patients with increased HDL-C possessed 19 DEGs with down-regulated APOA1 and HMGCR as gene signatures. With gene expression signatures, one standard deviation higher average gene expressions were associated with 5.1-, 48.8-, and 38.9-fold fewer CAD cases for three patient groups. As HDL-C increased in CAD patients, the expression of ABCG1 , CUBN , and HDLBP genes increased, while the expression of HMGCR and NPC2 genes, involved in cholesterol synthesis and trafficking, decreased. The expression of CD14 , CD36 , S100A8 , S100A9 , S100A12 , TLR5 , TLR8 , and VEGFA genes, involved in angiogenesis and inflammation mainly via nuclear factor-κB (NF-κB), decreased. Conclusions: The increased accumulation of cholesteryl ester in PBMC from patients with low HDL-C was suggested. This assumption contrasts with the suggested accumulation of free cholesterol in PBMC from patients with increased HDL-C, concomitant with suppression of cholesterol synthesis and traffic to the plasma membrane, and with an inflammatory state controlled by depressed CD36-mediated and upregulated apoE-mediated immunometabolic signaling. Gene signatures may be used for the diagnosis, prognosis, and treatment of CAD in dependence on HDL-C levels. (© 2024 The Author(s). Published by IMR Press.)
Databáze:	MEDLINE
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