HDL and Reverse Cholesterol Transport

Circ Res. 2019 May 10;124(10):1505-1518. doi: 10.1161/CIRCRESAHA.119.312617.


Cardiovascular disease, with atherosclerosis as the major underlying factor, remains the leading cause of death worldwide. It is well established that cholesterol ester-enriched foam cells are the hallmark of atherosclerotic plaques. Multiple lines of evidence support that enhancing foam cell cholesterol efflux by HDL (high-density lipoprotein) particles, the first step of reverse cholesterol transport (RCT), is a promising antiatherogenic strategy. Yet, excitement towards the therapeutic potential of manipulating RCT for the treatment of cardiovascular disease has faded because of the lack of the association between cardiovascular disease risk and what was typically measured in intervention trials, namely HDL cholesterol, which has an inconsistent relationship to HDL function and RCT. In this review, we will summarize some of the potential reasons for this inconsistency, update the mechanisms of RCT, and highlight conditions in which impaired HDL function or RCT contributes to vascular disease. On balance, the evidence still argues for further research to better understand how HDL functionality contributes to RCT to develop prevention and treatment strategies to reduce the risk of cardiovascular disease.

Keywords: atherosclerosis; cardiovascular diseases; cholesterol; diabetes mellitus; foam cells; reverse cholesterol transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / therapy*
  • Autophagy / physiology
  • Biological Transport
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / therapy*
  • Cholesterol / metabolism*
  • Diabetes Mellitus / metabolism
  • Foam Cells / metabolism*
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Lymphatic Vessels / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Plaque, Atherosclerotic / pathology


  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • Lipoproteins, HDL
  • Cholesterol