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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:88.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Transgenic Rabbits Expressing Human Apolipoprotein(a) Develop More Extensive Atherosclerotic Lesions in Response to a Cholesterol-Rich Diet

Jianglin Fan¹; Hiroaki Shimoyamada¹; Huijun Sun; Santica Marcovina; Kazuo Honda; Teruo Watanabe

From the Department of Pathology (J.F., H. Shimoyamada, H. Sun, T.W.), Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan; Northwest Lipid Research Laboratories (S.M.), University of Washington, Seattle; and the Research Institute of Yamonouchi Pharmaceutical Company (K.H.), Tsukuba, Japan.

Correspondence to Jianglin Fan, MD, PhD, Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575, Japan. E-mail J-LFAN{at}md.tsukuba.ac.jp

Abstract—High lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis. However, the relationship between Lp(a) and atherosclerosis is not fully understood. To examine the effect of Lp(a) on the development of atherosclerosis, we studied transgenic rabbits expressing human apolipoprotein(a) [apo(a)], which was assembled into Lp(a) in the plasma. Human apo(a) transgenic rabbits fed a 0.3% cholesterol diet for 16 weeks had more extensive atherosclerotic lesions than did nontransgenic rabbits, although the cholesterol levels in the plasma of both groups were similarly elevated. Compared with the lesions in control rabbits, the areas of the atherosclerotic lesions in human apo(a) transgenic rabbits were significantly increased in the aorta, the iliac artery, and the carotid artery. Furthermore, human apo(a) transgenic rabbits on a cholesterol-rich diet had a greater degree of coronary atherosclerosis than did control rabbits. Immunohistochemical analysis revealed that human apo(a) was frequently deposited in the atherosclerotic lesions of transgenic rabbits. We conclude that Lp(a) may have proatherogenic effects in the setting of a cholesterol-rich diet in transgenic rabbits.

Key Words: apolipoproteins • atherosclerosis • lipoproteins • transgenic rabbits

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