HIGH PLASMA HDL CONCENTRATIONS ASSOCIATED WITH ENHANCED ATHEROSCLEROSIS IN TRANSGENIC MICE OVEREXPRESSING LECITHIN-CHOLESTERYL ACYLTRANSFERASE

A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgen ic mouse model overexpressing human lecithin-cholesteryl acyltransfera se (LCAT) that has elevated HDL and increased diet-induced atheroscler osis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [H-3]cholesteryl ether incorporated in trans genic mouse HDL was reduced by 41% compared with control HDL, indicati ng ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential m echanism leading to increased atherosclerosis in the presence of high plasma HDL levels.