Atheroprotective mechanisms of HDL

Atherosclerosis. 1999 Jun;144(2):285-301. doi: 10.1016/s0021-9150(99)00065-9.


The aim of this review was to bring together results obtained from studies on different aspects of HDL as related to CHD and atherosclerosis. As atherosclerosis is a multistep process, the various components of HDL can intervene at different stages, such as induction of monocyte adhesion molecules, prevention of LDL modification and removal of excess cholesterol by reverse cholesterol transport. Transgenic technology has provided a model for atherosclerosis, and permitted evaluation of the contributions of different HDL components towards the global effect. The availability of apo AIV transgenic mice amplified the results obtained from apo AI overexpressors with respect to prevention of atherosclerosis. Prevention of atherosclerosis in apo E deficient mice by relatively small amounts of macrophage derived apo E may open new possibilities for therapeutic intervention. Contrary to early notions, increased plasma levels of CETP, even in the presence of low but functionally normal HDL, were atheroprotective. The extent to which paraoxonase and apo J participate in prevention of human atherosclerosis needs further evaluation. The findings that LCAT overexpression in rabbits was atheroprotective in contrast to increase in atherosclerosis in h LCAT tg mice, which was only partially corrected by CETP expression, call for some caution in the extrapolation of results from transgenic animals to humans. The important discovery of SR-BI as the receptor for selective uptake of CE from HDL revived interest in the clearance of CE from plasma. This pathway supplies also the vital precursor for steroidogenesis in adrenals and gonads and was shown to be dependent on apo AI.

Publication types

  • Review

MeSH terms

  • Animals
  • Apolipoproteins / blood
  • Arteriosclerosis / blood
  • Arteriosclerosis / genetics
  • Arteriosclerosis / prevention & control*
  • Carrier Proteins / blood
  • Cholesterol / blood
  • Cholesterol Ester Transfer Proteins
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / prevention & control
  • Glycoproteins*
  • Humans
  • Lipoproteins, HDL / blood*
  • Mice
  • Mice, Transgenic
  • Phospholipids / blood
  • Rabbits
  • Risk Factors


  • Apolipoproteins
  • CETP protein, human
  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Glycoproteins
  • Lipoproteins, HDL
  • Phospholipids
  • Cholesterol