on October 21, 2004
Published online before print October 21, 2004, doi: 10.1161/01.ATV.0000148404.24271.fc
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Submitted on August 5, 2004
Accepted on October 5, 2004
Oral Flavonoid Supplementation Attenuates Atherosclerosis Development in Apolipoprotein E-Deficient Mice
Keiichi Hishikawa *;
From the Departments of Clinical Renal Regeneration and Internal Medicine (K.H., T.F.), Division of Nephrology and Endocrinology, University of Tokyo, Japan; and the Department of Pharmacology (T.N.), Teikyo University School of Medicine, Japan.
* To whom correspondence should be addressed. E-mail: hishikawa-tky{at}umin.ac.jp.
Objective--Caffeic acid phenethyl ester (CAPE), a natural flavonoid, specifically blocks activation of nuclear factor-
B (NF-B). We examined the effects of oral CAPE supplementation on atherogenesis in apolipoprotein E-deficient (apoE-/-) mice.
Methods and Results--Ten-week-old male apoE-/- mice were supplemented orally with CAPE (30 mg/kg body weight) for 12 weeks. At the end of administration, atherosclerosis progression, NF-B activity, gene expression profiling by microarray analysis, and oxidative stress were studied. Treatment of apoE-/- mice with CAPE significantly reduced aortic atherosclerosis, NF-B activity, and expression of NF-B-related genes in the aorta. Moreover, expression of other gene clusters such as basic transcription factors, growth factors, cytokines, cell adhesion proteins, and extracellular matrix were also significantly reduced by treatment with CAPE. Plasma isoprostane level in apoE-/- mice was also significantly reduced by CAPE.
Conclusion--In apoE-/- mice, oral CAPE supplementation attenuates the atherosclerotic process. This may be attributable to direct inhibition of NF-B in the lesion and reduction of systemic oxidative stress.
Key words: atherosclerosis • NF-
B •
microarray •
oxidative stress •
flavonoid
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