Atherosclerosis is a chronic disease characterized by the deposition of excessive cholesterol in the arterial intima. Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. The generation of these cells is associated with imbalance of cholesterol influx, esterification and efflux. CD36 and scavenger receptor class A (SR-A) are mainly responsible for uptake of lipoprotein-derived cholesterol by macrophages. Acyl coenzyme A:cholesterol acyltransferase-1 (ACAT1) and neutral cholesteryl ester hydrolase (nCEH) regulate cholesterol esterification. ATP-binding cassette transporters A1(ABCA1), ABCG1 and scavenger receptor BI (SR-BI) play crucial roles in macrophage cholesterol export. When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plaque. The aim of this review is to describe what is known about the mechanisms of cholesterol uptake, esterification and release in macrophages. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis.
Keywords: ABCA1; ABCG1; ACAT1; AGE; ATP-binding cassette transporter A1; ATP-binding cassette transporter G1; Atherosclerosis; CD36; CE; ERK1/2; FC; Foam cells; HDL; LDLR; LXR; MAPK; PI3K; PKB; PKC; PPAR response elements; PPAR-γ; PPREs; RCT; RXR; SR-A; SR-BI; TGF-β; acyl coenzyme A:cholesterol acyltransferase-1; advanced glycation end products; apoA-I; apoE; apolipoprotein A-I; apolipoprotein E; cholesterol ester; extracellular signal-regulated kinases 1 and 2; free cholesterol; high-density lipoprotein; liver X receptor; low-density lipoprotein receptor; mitogen-activated protein kinase; nCEH; neutral cholesteryl ester hydrolase; ox-LDL; oxidized low-density lipoprotein; peroxisome proliferator-activated receptor-γ; phosphatidylinositol 3-kinase; protein kinase B; protein kinase C; retinoid X receptor; reverse cholesterol transport; scavenger receptor BI; scavenger receptor class A; transforming growth factor-β.
Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.