Endocrinol Metab.  2017 Mar;32(1):41-46. 10.3803/EnM.2017.32.1.41.

The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

• Jeong SJ
• Lee MN
• Oh GT

• KMID: 2413285
• DOI: http://doi.org/10.3803/EnM.2017.32.1.41

Abstract

Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

Keyword

Atherosclerosis; Cholesterol efflux; Lipophagy; Macrophages; Reverse cholesterol transport

MeSH Terms

Atherosclerosis
Autophagy
Cholesterol*
Foam Cells
Homeostasis
Hydrolysis
Lipid Droplets
Lysosomes
Macrophages*
Cholesterol

Figure

• 

  Fig. 1 Overview of the pathways of macrophage lipoprotein uptake and efflux. Macrophages uptake very low density lipoprotein (VLDL) and modified low density lipoprotein (LDL), such as oxidized (Ox) LDL via scavenger receptors (SRs, including by SR-A1 and cluster of differentiation 36 [CD36]). The internalized LDL is esterified by acetyl-coenzyme A acetyltransferases (ACAT1) and stored in lipid droplets (LDs). Neutral and acid lipolysis contribute to the release of cholesteryl ester (CE) for efflux in LDs via neutral CE hydrolase or lipophagy through lysosomal acid lipase (LAL). The cellular free cholesterol activates the liver X receptor (LXR)-retinoid X receptor (RXR) heterodimeric transcription factor that upregulates expression of ATP-binding cassette subfamily A member 1 (ABCA1). This transporter mediates the free cholesterol efflux from macrophages, with lipid-poor apolipoprotein A1 (apoA1) used as an acceptor. By reducing the accumulation of cholesterol in the wall of arteries via macrophage cholesterol efflux, reverse cholesterol transport may the prevent development of atherosclerosis. ER, endoplasmic reticulum; HDL, high density lipoprotein.

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