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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1871.)
© 2005 American Heart Association, Inc.

Vascular Biology

Critical Role of Mst1 in Vascular Remodeling After Injury

Hiroki Ono; Toshihiro Ichiki; Hideki Ohtsubo; Kae Fukuyama; Ikuyo Imayama; Yasuko Hashiguchi; Junichi Sadoshima; Kenji Sunagawa

From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; and the Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, Newark.

Correspondence to Toshihiro Ichiki, MD, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan. E-mail ichiki{at}cardiol.med.kyushu-u.ac.jp

Objective— Apoptosis of vascular smooth muscle cells (VSMCs) is observed in chronic vascular lesions such as atherosclerotic plaques and is believed to contribute to the vascular remodeling process. Mst1 is a ubiquitously expressed serine/threonine kinase known to be activated in response to a wide variety of nonphysiological apoptotic stimuli. However, little is known of the physiological function of Mst1, and its role in VSMCs has never been examined.

Methods and Results— Treatment of VSMCs with staurosporine induced apoptosis and cleavage of Mst1, which is a marker of its activation, as well as activation of caspase 3. Adenovirus-mediated overexpression of wild-type Mst1 (AdMst1) in VSMCs increased apoptotic cells with activation of caspase 3. Mst1 was induced and activated in the balloon-injured rat carotid artery. Infection with AdMst1 in balloon-injured rat carotid artery suppressed neointimal formation compared with infection with AdLacZ. Infection with AdMst1 significantly increased the apoptotic cell number in the neointima compared with infection with AdLacZ without affecting BrdU incorporation.

Conclusion— Our results suggest that Mst1 plays an important role in the induction of apoptosis of VSMCs, mediating the vascular remodeling process, and may be a potential therapeutic target for vascular proliferative diseases.

Apoptosis of vascular smooth muscle cells (VSMCs) is believed to contribute to the vascular remodeling process. Mst1 mediated VSMC apoptosis in vitro and vivo and suppressed neointimal formation in balloon-injured artery, suggesting that Mst1 mediates the vascular remodeling process and may be a potential therapeutic target for vascular proliferative diseases.

Key Words: Mst1 • caspase 3 • apoptosis • vascular smooth muscle cell • balloon injury

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