Abstract

To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis. Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database. Among 22 HDL-related genes, the transcript levels for 10 genes (ABCA1, BMP1, CUBN, HDLBP, LCAT, LDLR, PRKACB, PRKACG, SCARB1 and ZDHHC8) negatively correlated with HDL-C, while positively for APOA1 gene. Among 41 atherosclerosis-prone genes, the transcript levels for 11 genes (CSF1R, CSF2RB, IL18R1, ITGAM, ITGB3, PRKCQ, SREBF1, TLR5, TLR8, TNFRSF1A and TNFRSF1B) negatively correlated with HDL-C only, not with LDL-C and plasma TG. The protein products efficiently interacted within each cluster while only two intersection nodes existed between clusters. Coordinate regulation of cholesterol influx and efflux in PBMC in atherosclerosis-free subjects with widely varied HDL-C level is suggested. The decreased synthesis and transport of cholesteryl ester to the liver may contribute to hyperalphalipoproteinemia. HDL-C increase is associated with the decrease of expression of innate immunity and inflammation genes. Visualization of 22 responder genes is suggested to be useful in the validation of HDL functionality and atherogenesis even at the absence of morphologically evident coronary stenosis.

Highlights

  • Coronary heart disease is one of the major mortality causes around the globe [1]

  • The aim of the present study is to reveal the association of plasma level of high-density lipoprotein cholesterol level with the transcript level of selected genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis

  • We described earlier the primers for three housekeeping Glyceraldehyde3-phosphate dehydrogenase (GAPDH), Ribosomal protein L3 (RPL3) and Lactate dehydrogenase A (LDHA) genes and for twenty HDLrelated genes ATP binding cassette subfamily A member 1 (ABCA1), ATP binding cassette subfamily G member 1 (ABCG1), Scavenger receptor class B member 1 (SCARB1), Cholesteryl ester transfer protein (CETP), Protein kinase cAMP-activated catalytic subunit alpha (PRKACA), Protein kinase cAMP-activated catalytic subunit beta (PRKACB), Protein kinase cAMP-activated catalytic subunit gamma (PRKACG), Lecithin-cholesterol acyltransferase (LCAT), High density lipoprotein binding protein (HDLBP), Zinc finger DHHC-type containing 8 (ZDHHC8), A2M, associated transmembrane protein (AMN), ALB, CUBN, Bone morphogenetic protein 1 (BMP1), Lipoprotein lipase (LPL), Phospholipid transfer protein (PLTP), Apolipoprotein A1 (APOA1), Apolipoprotein E (APOE) and Apolipoprotein C2 (APOC2) [14]

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Summary

Introduction

Coronary heart disease is one of the major mortality causes around the globe [1]. The primary goal in the treatment of atherogenic dyslipidemia was to decrease the low-density lipoprotein cholesterol (LDL-C) and to increase high-density lipoprotein cholesterol (HDL-C). Some genetic and clinical data challenged the atheroprotective significance of circulating HDL. The functional mutations of ABCA1 gene with low HDL-C levels did not increase the risk of coronary heart disease [7], while the increase of HDL-C level did not decrease the risk [8] and even increased it in some circumstances. The loss of the atheroprotective properties of HDL may be related to their functional properties, not with their concentration [10]. The epidemiology, genetics, clinical and experimental data accumulated up to date do not unequivocally relate HDL-C as an anti-atherogenic factor

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