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Updated: Aug 17, 2026

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
Critical role of Mst1 in vascular remodeling after injury
Hiroki Ono1, Toshihiro Ichiki, Hideki Ohtsubo
1Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 812-8582 Fukuoka, Japan.
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.
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.
Insights
Mst1 kinase induces apoptosis in vascular smooth muscle cells (VSMCs), reducing vascular remodeling in disease. This finding highlights Mst1 as a therapeutic target for vascular proliferative conditions.
Area of Science:
- Vascular Biology
- Cell Death Pathways
- Molecular Medicine
Background:
- Vascular smooth muscle cell (VSMC) apoptosis contributes to chronic vascular lesions and remodeling.
- Mst1 kinase is activated by apoptotic stimuli, but its physiological role in VSMCs is unknown.
Purpose of the Study:
- To investigate the role of Mst1 in VSMC apoptosis and vascular remodeling.
- To determine if Mst1 is a potential therapeutic target for vascular proliferative diseases.
Main Methods:
- VSMCs were treated with staurosporine to induce apoptosis and Mst1 activation.
- Adenovirus-mediated overexpression of Mst1 (AdMst1) was used in VSMCs and balloon-injured rat carotid arteries.
- Neointimal formation and apoptosis were assessed in injured arteries.
Main Results:
- Staurosporine induced VSMC apoptosis, Mst1 cleavage, and caspase 3 activation.
- AdMst1 overexpression in VSMCs increased apoptosis and caspase 3 activation.
- AdMst1 suppressed neointimal formation in injured rat carotid arteries by increasing VSMC apoptosis without affecting proliferation.
Conclusions:
- Mst1 induces apoptosis in VSMCs, playing a key role in vascular remodeling.
- Mst1 represents a potential therapeutic target for vascular proliferative diseases like atherosclerosis.
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