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(Circulation. 1996;94:713-717.)
© 1996 American Heart Association, Inc.
Articles |
Inhibition of Atherosclerosis Development in Cholesterol-Fed Human Apolipoprotein A-I–Transgenic Rabbits
Rhone-Poulenc Rorer-Gencell division (N.D., F.E., J.-M.C., P.D.), Atherosclerosis Department, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France; Section of Experimental Atherosclerosis (H.K.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md; Institut National de la Recherche Agronomique (C.V., L.M.H.), Jouy en Josas, France; and INSERM 325, Institut Pasteur (G.C., A.T., C.F., J.C.F.), Lille, France.
Correspondence to Nicolas Duverger, PhD, Atherosclerosis Department, Centre de Recherche de Vitry-Alfortville, 13, Quai Jules Guesde-BP 14, 94403 Vitry sur Seine Cedex, France. E-mail nicolas.duverger@rp.fr.
Background Prospective epidemiological studies support the hypothesis that high levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I limit atherosclerosis development. However, more data from studies with animal models of atherosclerosis that resemble the human disease are required to demonstrate the effect of apo A-I in the inhibition of atherogenesis. The rabbit is a good animal model for human atherosclerosis.
Methods and Results Human apo A-I–transgenic rabbits have been produced, and we have evaluated the effect of apo A-I on the development of atherosclerosis in transgenic rabbits fed a cholesterol-rich diet for 14 weeks. Plasma cholesterol levels of atherogenic apo B-containing lipoproteins were similar for transgenic and control rabbits (>1000 mg/dL), while plasma levels of HDL cholesterol in the transgenic group were always about twice that of the control group (68±11 versus 37±3 mg/dL at 14 weeks; P<.001). At the end of the experiment, the amount of aortic surface area covered by lesions as well as the amount of lipid accumulation in the aorta were significantly less in transgenic rabbits compared with the control group (15±12% versus 30±8%, P<.0027 for the surface area of the thoracic aorta; 116±31 versus 247±39 µmol/g aorta, P<.0068 for cholesterol content in total aorta).
Conclusions Overexpression of human apo A-I in rabbits inhibits the development of atherosclerosis in this animal model that resembles, in many respects, human atherosclerosis.
Key Words: apolipoproteins • atherosclerosis • lipoproteins • cholesterol
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