Critical role of Mst1 in vascular remodeling after injury.
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.


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.


CONCLUSIONS
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.
Ono
Hiroki
H
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 812-8582 Fukuoka, Japan.
Ichiki
Toshihiro
T
Ohtsubo
Hideki
H
Fukuyama
Kae
K
Imayama
Ikuyo
I
Hashiguchi
Yasuko
Y
Sadoshima
Junichi
J
Sunagawa
Kenji
K
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D017209:Apoptosis / Q000502:physiology; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000473:pathology* / Q000503:physiopathology*; D002404:Catheterization / Q000009:adverse effects; D002478:Cells, Cultured; D015870:Gene Expression; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology
D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D020928:Mitogen-Activated Protein Kinases