Clearance of subcutaneous implants of cholesterol in the rat promoted by oxidation products of cholesterol. A postulated role for oxysterols in preventing atherosclerosis.
Cholesterol in crystalline form cannot be readily cleared from tissue and in this form it is sclerogenic. Phospholipids can solubilise cholesterol, promote its clearance and reduce the sclerosis. The phospholipids accompanying cholesterol deposited in atherogenesis are not adequate to solubilise all the cholesterol. It has been found that some oxidation products of cholesterol act synergistically with phosphatidylcholine to enhance the solubility of cholesterol in vitro. The effect of these oxysterols on solubilisation and clearance of cholesterol in vivo was examined in rats by implanting subcutaneously tablets made of cholesterol, cholesterol plus oxysterols and both with phosphatidylcholine. Tablets containing oxysterols went into solution rapidly, were cleared completely and allowed regression of the initial fibrosis promoted by the sterol without needing exogenous phospholipid. Solubilisation and clearance seem to have been affected by endogenous phospholipid, possibly high density lipoproteins, and by macrophages. Tablets without oxysterols showed no clearance at all but were cleared in part when phosphatidylcholine was added. Oxidation products of cholesterol form readily in foods of animal origin when suitably exposed to light and air. It is suggested that technology designed to prevent spoilage of foods has inadvertently resulted in the elimination from the Western diet of compounds which prevent the accumulation of cholesterol in the arterial wall.
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism*; D004343:Drug Implants; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013261:Sterols / Q000502:physiology*; D013607:Tablets
D004343:Drug Implants; D013261:Sterols; D013607:Tablets; D002784:Cholesterol