HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms

Nat Rev Cardiol. 2011 Apr;8(4):222-32. doi: 10.1038/nrcardio.2010.222. Epub 2011 Feb 8.


The lipoprotein HDL has two important roles: first, it promotes reverse cholesterol transport, and second, it modulates inflammation. Epidemiological studies show that HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. However, many patients who experience a clinical event have normal, or even high, levels of HDL cholesterol. Measuring HDL-cholesterol levels provides information about the size of the HDL pool, but does not predict HDL composition or function. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a proinflammatory particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Robust assays to evaluate the function of HDL are needed to supplement the measurement of HDL-cholesterol levels in the clinic.

Publication types

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

MeSH terms

  • Apolipoprotein A-I / metabolism
  • Cardiovascular Diseases / pathology*
  • Cholesterol, HDL / metabolism*
  • Cholesterol, HDL / physiology
  • Cholesterol, LDL / metabolism*
  • Cholesterol, LDL / physiology
  • Humans
  • Inflammation / pathology
  • Oxidative Stress
  • Risk Assessment
  • Risk Factors


  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Cholesterol, LDL