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

Abstract

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