Biological effects of oxysterols: current status.

A review of relevant literature on biological activities of oxysterols (OS) and cholesterol is presented. The data clearly demonstrate manifold biological activities, often detrimental, for OS compared with little or no such activity of a deleterious nature for cholesterol itself. Cholesterol is perhaps the single most important compound in animal tissue and, as such, it is difficult to imagine it as a toxin or hazard. In contrast, OS exhibit cytotoxicity to a wide variety of cells leading to angiotoxic and atherogenic effects; alter vascular permeability to albumin; alter prostaglandin synthesis and stimulate platelet aggregation, an important process facilitating atherosclerosis and thrombosis; alter the functionality of low density lipoprotein (LDL) receptors, possibly stimulating hypercholesterolaemia; modify cholesteryl ester accumulation in various cells, inducing foam cell formation; and enrich the LDL particle in cholesteryl esters, possibly increasing its atherogenicity. Furthermore, OS are mutagenic and carcinogenic, although some have been studied as antitumour agents based on their cytotoxic properties. Moreover, numerous studies have implicated OS in membrane and enzyme alterations that are interrelated with many of the foregoing effects. The authors find that OS deserve much more attention than cholesterol itself in terms of research activity but that unfortunately the reverse is true with regard to funding.