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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2453.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Decreased Susceptibility to Diet-Induced Atherosclerosis in Human Apolipoprotein A-II Transgenic Mice

Anne Tailleux; Muriel Bouly; Gérald Luc; Graciela Castro; Jean-Michel Caillaud; Nathalie Hennuyer; Philippe Poulain; Jean-Charles Fruchart; Nicolas Duverger; Catherine Fiévet

From Département d’athérosclérose et INSERM U. 325 (A.T., M.B., G.L., G.C., N.H., P.P., J.-C.F., C.F.), Institut Pasteur, Lille, France, and Rhône-Poulenc Rorer-Gencell Division (J.-M.C., N.D.), Atherosclerosis Department, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.

Correspondence to Anne Tailleux, PhD, Département d’athérosclérose et INSERM U. 325, Institut Pasteur, 1, rue du Professeur Calmette, 59019 Lille Cedex, France. E-mail Anne.Tailleux{at}pasteur-lille.fr

Abstract—Studies performed in vivo have been controversial regarding the implication of human apolipoprotein (apo)A-II in the atherogenic process. Expression of human apoA-II in transgenic mice fed a chow diet leads to (1) a bimodal distribution of high density lipoprotein (HDL) size as in humans, (2) a reduction in total cholesterol concentration that is mainly due to a reduction in non–HDL cholesterol level, and (3) a dramatic reduction in mouse endogenous apoA-I and apoA-II. After 20 weeks on an atherogenic diet, transgenic mice had reduced total cholesterol concentrations because of a reduction in cholesterol associated with all lipoprotein classes. Endogenous apoA-I and apoA-II were also dramatically decreased in transgenic mice. The mean area of atherosclerotic lesions was drastically decreased in transgenic mice (-44%, P=0.0027) compared with control mice. The amount of aortic surface covered by lesions was positively correlated with very low density lipoprotein cholesterol (P<0.01) and intermediate density lipoprotein cholesterol levels (P<0.05). Transgenic mice were protected against the development of atherosclerosis despite a marked decrease in HDL cholesterol and apoA-I concentrations. This protection may be related to the marked reduction in circulating low density lipoprotein (very low density and intermediate density lipoprotein) levels in transgenic mice.

Key Words: atherosclerosis • transgenic mice • lipoproteins

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