Nature Medicine
3, 744 - 749 (1997)
doi:10.1038/nm0797-744
High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithinchoesteryl acyltransferaseAnnie M. Bérard1, Bernhard Föger1, Alan Remaley1, Robert Shamburek1, Boris L. Vaisman1, Glenda Talley1, Beverly Paigen2, Robert F. Hoyt Jr.3, Santica Marcovina4, H. Bryan Brewer Jr.1
& Silvia Santamarina-Fojo1
1Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N115, 10 Center Drive, Bethesda, Maryland 20892-1666
2The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609-1500
3Laboratory of Animal Medicine and Surger, NHLBI, National Institutes of Health, Bethesda, Maryland 20892
4Northwestern Lipid Research Laboratories, University of Washington, 2121 North 35th Street, Seattle, Washington 98103 Correspondence should be addressed to S.S.-F 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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