title: 7-Ketocholesterol.
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.
authors.affiliation: Cell Biology Group, Heart Research Institute, Camperdown, NSW, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Lyons
authors.forename: A J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D006801:Humans; D007653:Ketocholesterols / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology; D008954:Models, Biological
chemical_list: D007653:Ketocholesterols; C003001:7-ketocholesterol