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. MstI 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 MstI, and its role in VSMCs has never been examined.

Methods and Results--Treatment of VSMCs with staurosporine induced apoptosis and cleavage of MstI, which is a marker of its activation, as well as activation of caspase 3. Adenovirus-mediated overexpression of wild-type MstI (AdMst1) in VSMCs increased apoptotic cells with activation of caspase 3. MstI 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 MstI 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.