Open AccessMacrophage‐mediated cholesterol handling in atherosclerosis
Author(s) -
Chistiakov Dimitry A.,
Bobryshev Yuri V.,
Orekhov Alexander N.
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12689
Subject(s) - cholesterol , scavenger receptor , cholesteryl ester , sterol o acyltransferase , chemistry , reverse cholesterol transport , biochemistry , endoplasmic reticulum , foam cell , macrophage , endosome , intermediate density lipoprotein , pinocytosis , receptor , endocytosis , lipoprotein , very low density lipoprotein , in vitro
Formation of foam cells is a hallmark at the initial stages of atherosclerosis. Monocytes attracted by pro‐inflammatory stimuli attach to the inflamed vascular endothelium and penetrate to the arterial intima where they differentiate to macrophages. Intimal macrophages phagocytize oxidized low‐density lipoproteins (ox LDL ). Several scavenger receptors ( SR ), including CD 36, SR ‐A1 and lectin‐like ox LDL receptor‐1 ( LOX ‐1), mediate ox LDL uptake. In late endosomes/lysosomes of macrophages, ox LDL are catabolysed. Lysosomal acid lipase ( LAL ) hydrolyses cholesterol esters that are enriched in LDL to free cholesterol and free fatty acids. In the endoplasmic reticulum ( ER ), acyl coenzyme A: cholesterol acyltransferase‐1 ( ACAT 1) in turn catalyses esterification of cholesterol to store cholesterol esters as lipid droplets in the ER of macrophages. Neutral cholesteryl ester hydrolases nCEH and NCEH 1 are involved in a secondary hydrolysis of cholesterol esters to liberate free cholesterol that could be then out‐flowed from macrophages by cholesterol ATP ‐binding cassette ( ABC ) transporters ABCA 1 and ABCG 1 and SR ‐ BI . In atherosclerosis, disruption of lipid homoeostasis in macrophages leads to cholesterol accumulation and formation of foam cells.