7-Ketocholesterol

Int J Biochem Cell Biol. Mar-Apr 1999;31(3-4):369-75. doi: 10.1016/s1357-2725(98)00123-x.

Abstract

7-Ketocholesterol is a major oxidation product of cholesterol found in human atherosclerotic plaque and is more atherogenic than cholesterol in some animal studies. 7-Ketocholesterol can inhibit cholesterol 7 alpha-hydroxylase, the rate-limiting step in bile acid biosynthesis, as well as strongly inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. It has even been suggested that 7-ketocholesterol is formed enzymically as an endogenous regulator of cholesterol biosynthesis. However, when tested as a pharmacological cholesterol-lowering agent, inhibition of HMG-CoA reductase was rapidly overcome and the 7-ketocholesterol metabolised. In vitro, 7-ketocholesterol has wide-ranging and potent effects, most of which have the potential to contribute to atherosclerosis. For example, 7-ketocholesterol can be cytotoxic and can induce apoptosis in vascular cells. These effects, either individually or more likely, in combination, all implicate 7-ketocholesterol in the initiation and development of atherosclerosis, but further work is needed to establish whether or not its role is a direct causal one.

Publication types

  • Review

MeSH terms

  • Humans
  • Ketocholesterols / biosynthesis
  • Ketocholesterols / chemistry*
  • Ketocholesterols / pharmacology
  • Ketocholesterols / physiology
  • Models, Biological

Substances

  • Ketocholesterols
  • 7-ketocholesterol