Published Online
on May 10, 2004

A more recent version of this article appeared on May 25, 2004

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Submitted on December 5, 2003
Accepted on February 6, 2004

Differential Effects of Green Tea-Derived Catechin on Developing Versus Established Atherosclerosis in Apolipoprotein E-Null Mice

Kuang-Yuh Chyu MD, PhD^*, Stephanie M. Babbidge BS, Xiaoning Zhao PhD, Ram Dandillaya MD, Anton G. Rietveld PhD, Juliana Yano BS, Paul Dimayuga PhD, Bojan Cercek MD, PhD, and Prediman K. Shah MD

From the Atherosclerosis Research Center, Division of Cardiology, and Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California, Los Angeles; and the Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, Netherlands (A.G.R.).

^* To whom correspondence should be addressed. E-mail: chyuk{at}cshs.org.

Background--Oxidative stress has been implicated in vascular injury and atherogenesis, and antioxidant treatment has shown favorable results in preclinical studies. Despite this, antioxidant therapy has failed to show benefit in clinical trials. Failure of antioxidants in clinical trials may be partly because such therapy is started after atherosclerosis is already well established, whereas the benefits in animal models may be results from early initiation of antioxidants while atherosclerosis is still evolving.

Methods and Results--To test this hypothesis, we evaluated the effect of epigallocatechin gallate (EGCG), the main antioxidant derived from green tea, on evolving and established atherosclerotic lesions in hypercholesterolemic apolipoprotein E-null mice. Established native aortic atherosclerotic lesions and evolving atherosclerotic lesions produced by periadventitial cuff injury to carotid arteries were assessed in mice after 21 and 42 days of treatment with daily intraperitoneal injections of EGCG (10 mg/kg) or PBS. EGCG treatment resulted in an increase in the antioxidant capacity in local vascular tissue and systemic circulation and reduced vascular smooth muscle cell proliferation and redox-sensitive gene activation in vitro. EGCG reduced cuff-induced evolving atherosclerotic plaque size at 21 and 42 days by 55% and 73%, respectively, compared with PBS treatment (P<0.05). Conversely, EGCG had no effect on established lesions in the aortic sinuses or the rest of the aorta.

Conclusions--Our data suggest that antioxidant EGCG differentially reduces evolving atherosclerotic lesions without influencing established atherosclerosis in the apolipoprotein E-null mice.

Key words: atherosclerosis • catechin • antioxidant

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