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Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice

Fukao, Hideharua; Ijiri, Yoshinobub; Miura, Mayukob; Hashimoto, Masarub; Yamashita, Tsutomub; Fukunaga, Chizuruc; Oiwa, Kazuhirod; Kawai, Yasuhiroe; Suwa, Makatoe; Yamamoto, Junichirob

Blood Coagulation & Fibrinolysis: August 2004 - Volume 15 - Issue 6 - p 441-446

Resveratrol is one of the major polyphenolics in red wine that has been shown to exert the preventive effects against cardiovascular diseases. The effect of trans-resveratrol (t-RES) administered as an ingredient of the diet on the atherothrombotic tendency was assessed in genetically hypercholesterolemic mice after laser-induced damage on endothelium. Mice lacking both apolipoprotein E and low-density lipoprotein receptor (apoE–/–/LDLR–/–) were fed with a high-fat diet with or without t-RES (9.6 and 96 mg/kg diet) for 8 weeks. The atherosclerotic tendency was morphometrically analyzed in their aortae. The thrombotic tendency was determined by inducing thrombus by the irradiation of a helium–neon laser on carotid arteries of these mice with injection of Evans blue. Atherosclerotic area and thrombus size were evaluated by image analyzing in a computer system. Even though the plasma concentrations of lipids (total cholesterol and triacylglycerol) did not change in the control and t-RES groups, a significant decrease (∼ 30%) in the formation of atheroma was observed in the aortae of the t-RES group. The size of laser-induced thrombus that mostly consisted of platelet aggregates was significantly reduced (∼ 25%) in the t-RES group compared with that in the control group. Thus, t-RES orally administrated with a high-fat diet in apoE–/–/LDLR–/– mice significantly suppressed atherosclerosis in their aortae and reduced the laser-induced thrombosis in their carotid arteries.

aDepartment of Nutritional Science, Faculty of Food Culture, Kurashiki Sakuyo University, Kurashiki, Japan, bLaboratory of Physiology, Faculty of Nutrition, and the High Technology Research Center, Kobe Gakuin University, Kobe, Japan, cKakogawa Synthetic Public Health Center, Kakogawa, Japan, dCommunications Research Laboratory, Kansai Advanced Research Center, Kobe, Japan and eDevelopment Department, Health and Beauty Head Quarter, Sunstar Inc., Osaka, Japan.

Correspondence and requests for reprints to H. Fukao, Ph.D., Department of Nutritional Science, Faculty of Food Culture, Kurashiki Sakuyo University, 3515 Nagao, Tamashima, Kurashiki city, Okayama, 710-0292 Japan. Tel: +81 86 523 0821; fax: +81 86 523 0814; e-mail:

Received 28 July 2003 Revised 28 February 2004 Accepted 1 March 2004

© 2004 Lippincott Williams & Wilkins, Inc.