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(Circulation. 2003;107:679.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Osteopontin Transgenic Mice Fed a High-Cholesterol Diet Develop Early Fatty-Streak Lesions

Kikuo Isoda, MD, PhD; Yashuhiro Kamezawa, MD; Makoto Ayaori, MD; Masatoshi Kusuhara, MD, PhD; Norihiro Tada, PhD; Fumitaka Ohsuzu, MD, PhD

From Internal Medicine I, National Defense Medical College (K.I., Y.K., M.A., M.K., F.O.), Tokorozawa, Japan, and the Division of Biomedical Research Resources, Juntendo University School of Medicine (N.T.), Tokyo, Japan.

Correspondence to Kikuo Isoda, MD, PhD, Internal Medicine I, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359-8513, Japan. E-mail isoda{at}me.ndmc.ac.jp

Background— Osteopontin (OPN) is a noncollagenous adhesion protein found at the site of atherosclerotic lesions. However, it has not yet been clarified whether or not OPN can promote atherosclerotic lesions.

Methods and Results— We investigated the contribution of OPN to atherosclerosis by evaluating aortic sinus lesions of both OPN transgenic (Tg) and non-Tg mice fed an atherogenic diet (1.25% cholesterol) for 16 weeks. The atherosclerotic lesions were found to be significantly larger in OPN-Tg compared with those in non-Tg (17 859±2010 versus 6469±485 µm², P<0.01). The lesions in both mice were fatty-streak lesions with an accumulation of mononuclear cells and lipids. We next investigated the production of interleukin (IL)-10 by macrophages from both mice. Compared with the non-Tg mice, a 42% (P<0.01) and 73% (P<0.001) decrease in the IL-10 production was identified in the OPN-Tg mice either without or with lipopolysaccharide.

Conclusions— The expression of OPN induces fatty-streak lesion formation in mice fed an atherogenic diet and inhibits IL-10 production by macrophages, thus suggesting that OPN plays an important role in the development of fatty-streak lesions in vivo.

Key Words: atherosclerosis • genes • interleukins

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