High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithinchoesteryl acyltransferase
- 1 July 1997
- journal article
- Published by Springer Nature in Nature Medicine
- Vol. 3 (7) , 744-749
- https://doi.org/10.1038/nm0797-744
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.Keywords
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