MST1 down-regulation in decreasing apoptosis of aortic dissection smooth muscle cell apoptosis

Y. Shi, B. Liu, C.-S. Wang, C.-S. Yang

Department of Cardiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. chunsongwangr@126.com

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• Cardiology

OBJECTIVE: Elevated apoptosis of vascular smooth muscle cell (VSMC) is correlated with the occurrence of aortic dissection (AD). Mammalian ste20-like protein kinase 1 (MST1) is one important component of Hippo-YAP signal pathway for activation and cell apoptosis facilitation. Whether MST1 plays a role in AD pathogenesis is unclear yet. This study established an AD rat model to investigate the role of MST1 in regulating VSMC apoptosis and AD pathogenesis.

MATERIALS AND METHODS: Cell apoptosis was compared between AD vascular tissues and normal rats, in addition to Caspase-3 activity, and expression of MST1, p-LATS1, p-YAP1, YAP1. In vitro cultured VSMCs from AD rats were treated with siRNA-MST1 to test apoptotic rate and Caspase-3 activity. AD model rats were treated with pGLVU6/GFP-MST1 for comparing MST1, p-LATS1, p-YAP1, and YAP1 expression, along with Caspase-3 activity, cell apoptosis, AD formation rate, diameter, and length.

RESULTS: Compared to control group, AD rats had elevated vascular cell apoptosis, Caspase-3 activity, expressions of MST1, p-LATS1, and p-YAP1, plus lower YAP1 expression. siRNA interference of MST1 significantly inhibited apoptosis of in vitro cultured VSMC. shRNA lentivirus targeting MST1 pGLVU6/GFP-MST1 remarkably decreased expression of MST1, p-LATS1, and p-YAP1 in AD rat vascular tissues, increased YAP1 expression, decreased VSMC apoptosis, AD formation rate, AD diameter/length.

CONCLUSIONS: MST1 up-regulation plays a role in facilitating VSMC apoptosis and AD pathogenesis. Down-regulation of MST1 decreased VSMC apoptosis and AD formation.

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