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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1573.)
© 2002 American Heart Association, Inc.

Vascular Biology

Fibrillar Collagen Regulation of Plasminogen Activator Inhibitor-1 Is Involved in Altered Smooth Muscle Cell Migration

Shinji Tanaka; Hidenori Koyama; Takuya Ichii; Atsushi Shioi; Masayuki Hosoi; Elaine W. Raines; Yoshiki Nishizawa

From the Department of Metabolism, Endocrinology, and Molecular Medicine (S.T., H.K., T.I., M.H., Y.N.) and the Department of Cardiovascular Medicine (A.S.), Osaka City University Graduate School of Medicine, Osaka, Japan, and the Department of Pathology (E.W.R.), University of Washington, Harborview Medical Center, Seattle.

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

Objective— Vascular smooth muscle cells (SMCs) cultured on polymerized type I collagen fibrils are arrested in the G₁ phase of the cell cycle, and their phenotypic markers and pattern of expressed genes are markedly altered. In this study, we examined polymerized collagen regulation of plasminogen activator inhibitor (PAI)-1 and its involvement in SMC migration.

Methods and Results— We demonstrate that secretion and cell surface accumulation of PAI-1 are suppressed in SMCs cultured on polymerized collagen compared with SMCs cultured on monomer collagen. SMCs replated on vitronectin after culture on monomer collagen result in PAI-1 accumulation at focal adhesions and colocalization with _vß₃ integrins. In contrast, polymerized collagen inhibits PAI-1 accumulation at focal adhesions when the SMCs are replated on vitronectin. Furthermore, for SMCs cultured on polymerized collagen, platelet-derived growth factor-stimulated migration on vitronectin is enhanced by PAI-1, with its function counteracted by urinary plasminogen activator. Finally, exogenous addition of PAI-1 appears to partly restore platelet-derived growth factor-stimulated _vß₃-dependent SMC migration that is specifically suppressed by polymerized collagen.

Conclusions— Polymerized type I collagen fibrils dynamically regulate PAI-1, which may be involved in altered _vß₃ integrin-dependent SMC migration.

Key Words: atherosclerosis • vascular remodeling • extracellular matrix • _vß₃ integrin • platelet-derived growth factor

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