Lamin A/C negatively regulated by miR-124-3p modulates apoptosis of vascular smooth muscle cells during cyclic stretch application in rats.

Apoptosis of vascular smooth muscle cells (VSMCs) influenced by abnormal cyclic stretch is crucial for vascular remodeling during hypertension. Lamin A/C, a nuclear envelope protein, is mechano-responsive, but the role of lamin A/C in VSMC apoptosis is still unclear.FX-5000T Strain Unit provided cyclic stretch (CS) in vitro. AnnexinV/PI and cleaved Caspase 3 ELISA detected apoptosis. qPCR was used to investigate expression of miR-124-3p and a luciferase reporter assay was used to evaluate the ability of miR-124-3p binding to the Lmna 3'UTR. Protein changes of lamin A/C and relevant molecules were detected by western blot. Ingenuity Pathway Analysis and Protein/DNA array detected the potential transcription factors. Renal hypertensive rats verified these changes.High cyclic stretch (15%-CS) induced VSMC apoptosis and repressed lamin A/C expressions compared with normal (5%-CS) control. Downregulation of lamin A/C enhanced VSMC apoptosis. In addition, 15%-CS had no significant effect on mRNA expression of Lmna, and lamin A/C degradation was not induced by autophagy. 15%-CS elevated miR-124-3p, which bound to 3'UTR of Lmna, and then negatively regulated protein expression of lamin A/C. Similar changes occurred in renal hypertensive rats compared with sham controls. Lamin A/C repression affected activity of TP53, CREB1, MYC, STAT1/5/6 and JUN, which may in turn affect apoptosis.Our data suggested that the decreased expression of lamin A/C upon abnormal cyclic stretch and hypertension may induce VSMC apoptosis. These mechano-responsive factors play important roles in VSMC apoptosis and might be novel therapeutic targets for vascular remodeling in hypertension. This article is protected by copyright. All rights reserved.