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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1286.)
© 2002 American Heart Association, Inc.

Vascular Biology

Thrombospondin-1 Mediates Smooth Muscle Cell Proliferation Induced by Interaction With Human Platelets

Takuya Ichii; Hidenori Koyama; Shinji Tanaka; Atsushi Shioi; Yasuhisa Okuno; Shuzo Otani; Yoshiki Nishizawa

From the Department of Biochemistry (T.I., S.O.), the Department of Metabolism, Endocrinology, and Molecular Medicine (H.K., S.T., Y.N.), and the Department of Cardiovascular Medicine (A.S., Y.O.), Osaka City University Graduate School of Medicine, Osaka, Japan.

Correspondence to Hidenori Koyama, MD, PhD, Department of Metabolism, Endocrinology, and Molecular Medicine (Second Department of Internal Medicine), Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. E-mail hidekoyama{at}med.osaka-cu.ac.jp

Objectives— Platelet adherence and activation are associated with smooth muscle cell (SMC) proliferation and arterial restenosis. This study examined platelet-SMC interaction on fibrillar type I collagen and analyzed the role of thrombospondin (TSP)-1 in platelet-induced SMC proliferation.

Methods and Results— When SMCs cultured on fibrillar collagen were treated with human platelets (5 preparations), 7.45±2.94% of the cells passed through S phase within 24 hours, as determined by bromodeoxyuridine nuclear labeling. The addition of platelets markedly induced SMC TSP-1 mRNA expression and cell surface protein accumulation, which colocalized with adhered platelets, as determined by _IIb integrin immunostaining. Direct interaction of platelets with SMCs was necessary for its effect on proliferation and TSP-1 accumulation, as determined in the transwell culture system. The anti–TSP-1 blocking antibody strongly inhibited platelet-induced SMC proliferation by 60%. Analysis of the receptors for TSP-1 accumulation on the SMC surface revealed that ß₁ integrins are mainly involved. The anti–ß₁ integrin blocking antibody, which potently suppressed TSP-1 accumulation on SMCs, also markedly inhibited platelet-stimulated SMC proliferation.

Conclusions— TSP-1 and ß₁ integrin interaction is involved in platelet-stimulated SMC proliferation. This in vitro coculture system could prove useful for examining the molecular mechanism underlying platelet-induced vascular remodeling and for studying the mechanism of a tested drug for restenosis.

Key Words: atherosclerosis • platelet-derived factors • integrins • collagen (type I) • vascular injury

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