出版社：American Society for Biochemistry and Molecular Biology
摘要：LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [ Scarab (−/−)] mice, which have a secondary defect in cholesterol esterification. Scarab (−/−)×LCAT-null [ Lcat (−/−)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab (−/−)× LCAT -transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab (−/−)× LCAT -Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab (−/−)× LCAT -Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab (−/−) mice ( P
关键词：lecithin:cholesterol acyltransferase ; scavenger receptor class B member I ; knockout
