Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1.

摘要: Inhibitors of acyl CoA:cholesterol acyltransferase (ACAT) have attracted considerable interest as a potential treatment for atherosclerosis. Currently available inhibitors probably act nonselectively against the two known ACATs. One these enzymes, ACAT1, is highly expressed in macrophages atherosclerotic lesions, where it contributes to foam-cell formation. In this study, we examined effects selective ACAT1 deficiency mouse models setting severe hypercholesterolemia caused by apoE or LDL receptor (LDLR), total led marked alterations cholesterol homeostasis and extensive deposition unesterified skin brain. Bone marrow transplantation experiments demonstrated that was sufficient cause dermal xanthomas hyperlipidemic LDLR-deficient mice. did not prevent development lesions either apoE-deficient mice, despite causing relatively lower serum levels. However, ACAT1-deficient mice were atypical composition, with reduced amounts neutral lipids paucity advanced lesions. Although latter findings may be associated increased lesion stability, indicate selectively inhibiting hyperlipidemia detrimental consequences.