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(Circulation. 2004;110:141-148.)
© 2004 American Heart Association, Inc.

Original Articles

Inhibition of Platelet Adherence to Mononuclear Cells by -Tocopherol

Role of P-Selectin

Toyoaki Murohara, MD, PhD; Hisao Ikeda, MD, PhD; Yoritaka Otsuka, MD; Mika Aoki, BS; Nobuya Haramaki, MD, PhD; Atsushi Katoh, MD, PhD; Yoshinori Takajo, MD, PhD; Tsutomu Imaizumi, MD, PhD

From the Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan (T.M., M.A.); The Cardiovascular Research Institute, Kurume University, Kurume, Japan (H.I., N.H., A.K., Y.T., T.I.); and the Department of Cardiology, National Cardiovascular Center, Suita, Japan (Y.O.).

Correspondence to Dr Toyoaki Murohara, Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan. E-mail murohara{at}med.nagoya-u.ac.jp

Received May 9, 2001; de novo received December 27, 2003; revision received March 23, 2004; accepted March 24, 2004.

Background— Platelet-leukocyte interaction is an early important event for thrombogenesis, and this process is mainly mediated by P-selectin on platelets. Although -tocopherol has been shown to inhibit thrombotic disorders, the effect of -tocopherol on platelet P-selectin expression and platelet-leukocyte interaction is little known.

Methods and Results— We examined whether -tocopherol inhibited human platelet P-selectin expression and platelet-leukocyte interaction. -Tocopherol (50 to 500 µg/mL) inhibited thrombin-induced or phorbol 12-myristate 13-acetate (PMA)-induced P-selectin expression on platelets. -Tocopherol suppressed platelet–mononuclear cell (MNC) interaction, platelet aggregation, and platelet protein kinase C (PKC) activity stimulated with either PMA (100 nmol/L) or thrombin. Inhibitory actions of -tocopherol against the platelet functions were mimicked by staurosporine, a selective PKC inhibitor. After oral supplementation of -tocopherol (300 mg/d for 3 weeks) in healthy subjects, thrombin-mediated or PMA-mediated P-selectin expression, platelet-MNC interaction, and platelet aggregation ex vivo were suppressed.

Conclusions— -Tocopherol inhibited P-selectin expression on human platelets and thereby attenuated platelet-MNC interactions, which were mediated at least in part by the inhibition of intraplatelet PKC activity. These actions of -tocopherol on platelet functions provide new insights into the antithromboatherogenic properties of -tocopherol.

Key Words: thrombus • platelets • leukocytes • antioxidants • hemorrhage

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