Cholesterol efflux pathways, inflammation, and atherosclerosis

Plasma levels of high-density lipoprotein (HDL) inversely correlate with the incidence of cardiovascular diseases (CVD). The causal relationship between plasma HDL-cholesterol levels and CVD has been called into question by Mendelian randomization studies and the majority of clinical trials not show...

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Bibliographic Details
Published in:Critical reviews in biochemistry and molecular biology 2021-07, Vol.56 (4), p.426-439
Main Authors: Groenen, Anouk G., Halmos, Benedek, Tall, Alan R., Westerterp, Marit
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis
Atherosclerosis - genetics
Atherosclerosis - metabolism
Atherosclerosis - pathology
Biological Transport, Active - genetics
cardiovascular diseases
Cell Proliferation
cholesterol efflux
Cholesterol, HDL - genetics
Cholesterol, HDL - metabolism
Gene Expression Regulation
Hematopoietic Stem Cells - metabolism
Hematopoietic Stem Cells - pathology
high-density lipoprotein
Humans
Inflammasomes
inflammation
Inflammation - genetics
Inflammation - metabolism
Inflammation - pathology
Liver X Receptors - genetics
Liver X Receptors - metabolism
Mendelian Randomization Analysis
RNA-Seq
Single-Cell Analysis
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Summary:Plasma levels of high-density lipoprotein (HDL) inversely correlate with the incidence of cardiovascular diseases (CVD). The causal relationship between plasma HDL-cholesterol levels and CVD has been called into question by Mendelian randomization studies and the majority of clinical trials not showing any benefit of plasma HDL-cholesterol raising drugs on CVD. Nonetheless, recent Mendelian randomization studies including an increased number of CVD cases compared to earlier studies have confirmed that HDL-cholesterol levels and CVD are causally linked. Moreover, several studies in large population cohorts have shown that the cholesterol efflux capacity of HDL inversely correlates with CVD. Cholesterol efflux pathways exert anti-inflammatory and anti-atherogenic effects by suppressing proliferation of hematopoietic stem and progenitor cells, and inflammation and inflammasome activation in macrophages. Cholesterol efflux pathways also suppress the accumulation of cholesteryl esters in macrophages, i.e. macrophage foam cell formation. Recent single-cell RNASeq studies on atherosclerotic plaques have suggested that macrophage foam cells have lower expression of inflammatory genes than non-foam cells, probably reflecting liver X receptor activation, upregulation of ATP Binding Cassette A1 and G1 cholesterol transporters and suppression of inflammation. However, when these pathways are defective lesional foam cells may become pro-inflammatory.
ISSN:1040-9238
1549-7798
DOI:10.1080/10409238.2021.1925217