miR-4286/TGF-β1/Smad3-Negative Feedback Loop Ameliorated Vascular Endothelial Cell Damage by Attenuating Apoptosis...

Atherosclerosis (AS), known as the chronic inflammatory disease, results from the dysfunction of vascular endothelial cells (VECs). Transforming growth factor-β1 (TGF-β1) has been reported to be induced by oxidized low-density lipoprotein (ox-LDL) and contribute to AS-related vascular endothelial cell damage. This work planned to study the mechanism of TGF-β1 in vascular endothelial cell damage. We found that TGF-β1 was activated by ox-LDL in human umbilical vascular endothelial cells (HUVECs). Silence of TGF-β1 reversed the inductive effect of ox-LDL on apoptosis and inflammatory response of HUVECs. Mechanistically, microRNA-4286 (miR-4286) targeted and inhibited TGF-β1 to inhibit Smad3, and Smad3 bound to the promoter of miR-4286 to repress its transcription. Rescue assays indicated that miR-4286 ameliorated the ox-LDL-induced apoptosis and inflammatory response through inhibiting TGF-β1. In conclusion, our study first demonstrated that miR-4286/TGF-β1/Smad3-negative feedback loop ameliorated vascular endothelial cell damage by attenuating apoptosis and inflammatory response, providing new thoughts for promoting the treatment of AS.