Faculty Research 1990 - 1999

Title

High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase.

Document Type

Article

Publication Date

1997

Keywords

Aorta: pa, Atherosclerosis: bl, en, pa, Cholesterol, Diet-Atherogenic, Disease-Models-Animal, Female, Human, Lipids, Lipoproteins-HDL: bl, ph, Male, Mice, Mice-Transgenic, Phosphatidylcholine-Sterol-O-Acyltransferase: bi, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Nat Med 1997 Jul;3(7):744-9

Grant

HL30086/HL/NHLBI, HL32087/HL/NHLBI

Abstract

A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating 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 mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels.

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