Mechanical Stretch Induces Smooth Muscle Cell Dysfunction by Regulating ACE2 via P38/ATF3 and Post-transcriptional Regulation by miR-421
Xiaolin Liu, Xinxin Liu, Mengmeng Li, Yu Zhang, Weijia Chen, Meng Zhang, Cheng Zhang, Cheng Zhang, Mei Zhang, Mei Zhang
Abstract
. Overexpression was used to analyze the role of ACE2 played in the proliferation, migration, apoptosis, and collagen metabolism of the VSMCs. RT-qPCR, Western blot, luciferase assay, and ChIP assay were used to elucidate the molecular mechanism of ACE2 expression regulated by stretch. We found that mechanical stretch modulated the expression of the ACE2/Ang-(1-7) and ACE/AngII axis. ACE2 was mechanically sensitive and was involved in the stretch-induced dysfunction of VSMCs. The p38 MAPK/ATF3 pathway and miR-421 participated in the regulation of ACE2. Thus, ACE2 may contribute to the development of vascular remodeling under conditions of mechanical stretch.