Cholesterol synthesis and esterification in experimental xanthoma tissues.

We studied cholesterol metabolism in experimental xanthoma tissues which were induced by injection of high molecular weight sodium dextran sulfate into the dermis of hypercholesterolemic rabbits. Control studies were performed on dermal specimens of the dextran sulfate-injected site of normolipemic rabbits. Cholesterol accumulation was much greater in the hypercholesterolemic rabbit tissues than in the normolipemic rabbit tissues. Histiocytes and foam cells in such lesions had an ability to synthesize cholesterol. However, cholesterol synthesis was suppressed in the cholesterol-rich tissues of hypercholesterolemic rabbits. This suppression was obviously caused by the accumulation of cholesterol in the tissues which take up lipoprotein in hypercholesterolemic rabbits. On the other hand, esterification of cholesterol was greater in the hypercholesterolemic rabbit tissues than in the normolipemic rabbit tissues. Cholesterol was esterified more selectively with oleic acid than with palmitic acid. Therefore, cholesteryl oleate increased in the tissues concomitantly with the accumulation of cholesteryl esters. Fatty acids of serum origin rather than those synthesized in situ were more important in the esterification process. It was suggested that cholesterol esterification was mediated by acyl-coenzyme A:cholesterol acyltransferase and that lecithin:cholesterol acyltransferase contributed little to the process.