Oxysterols and atherosclerosis

Atherosclerosis. 1999 Jan;142(1):1-28. doi: 10.1016/s0021-9150(98)00196-8.


Oxysterols are present in human atherosclerotic plaque and are suggested to play an active role in plaque development. Moreover, the oxysterol:cholesterol ratio in plaque is much higher than in normal tissues or plasma. Oxysterols in plaque are derived both non-enzymically, either from the diet and/or from in vivo oxidation, or (e.g. 27-hydroxycholesterol) are formed enzymically during cholesterol catabolism. While undergoing many of the same reactions as cholesterol, such as being esterified by cells and in plasma, certain oxysterols in some animal and in vitro models exhibit far more potent effects than cholesterol per se. In vitro, oxysterols perturb several aspects of cellular cholesterol homeostasis (including cholesterol biosynthesis, esterification, and efflux), impair vascular reactivity and are cytotoxic and/or induce apoptosis. Injection of relatively large doses of oxysterols into animals causes acute angiotoxicity whereas oxysterol-feeding experiments have yielded contrary results as far as their atherogenicity is concerned. There is no direct evidence yet in humans that oxysterols contribute to atherogenesis. However, oxysterol levels are elevated in human low-density lipoprotein (LDL) subfractions that are considered potentially atherogenic and two recent studies have indicated that raised plasma levels of a specific oxysterol (7beta-hydroxycholesterol) may be associated with an increased risk of atherosclerosis. At the present time there are a number of significant and quite widespread problems with current literature which preclude more than a tentative suggestion that oxysterols have a causal role in atherogenesis. Further studies are necessary to definitively determine the role of oxysterols in atherosclerosis, and considering the wide-ranging tissue levels reported in the literature, special emphasis is needed on their accurate analysis, especially in view of the susceptibility of the parent cholesterol to artifactual oxidation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arteriosclerosis / physiopathology*
  • Cholestenones / metabolism
  • Cholestenones / pharmacology
  • Cholesterol / pharmacology
  • Cholesterol / physiology*
  • Cholesterol, Dietary / metabolism
  • Humans
  • Hydroxycholesterols / metabolism
  • Hydroxycholesterols / pharmacology


  • Cholestenones
  • Cholesterol, Dietary
  • Hydroxycholesterols
  • Cholesterol