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High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithinchoesteryl acyltransferase

Nature Medicine volume 3, pages 744–749 (1997)Cite this article

Abstract

A subset of patients with high plasma HDL concentration 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 mehanism leading to increased atherosclerosis in the presence of high plasma HDL levels.

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Authors and Affiliations

  1. Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N115, 10 Center Drive, Bethesda, Maryland, 20892-1666

    Annie M. Bérard, Bernhard Föger, Alan Remaley, Robert Shamburek, Boris L. Vaisman, Glenda Talley, H. Bryan Brewer Jr. & Silvia Santamarina-Fojo

  2. The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, 04609-1500

    Beverly Paigen

  3. Laboratory of Animal Medicine and Surger, NHLBI, National Institutes of Health, Bethesda, Maryland, 20892

    Robert F. Hoyt Jr.

  4. Northwestern Lipid Research Laboratories, University of Washington, 2121 North 35th Street, Seattle, Washington, 98103

    Santica Marcovina

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  1. Annie M. Bérard
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Bérard, A., Föger, B., Remaley, A. et al. High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithinchoesteryl acyltransferase. Nat Med 3, 744–749 (1997). https://doi.org/10.1038/nm0797-744

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