AREL1 resists the apoptosis induced by TGF-beta by inhibiting SMAC in vascular endothelial cells

Abnormal apoptosis of vascular endothelial cells is an important feature of arteriosclerosis (AS). Here, we induced apoptosis in human umbilical vein endothelial cells (HUVECs) using transforming growth factor-beta (TGF-beta), and investigated the role of antiapoptotic E3 ubiquitin ligase (AREL1) in the apoptosis of vascular endothelial cells. We proved that AREL1 is downregulated in TGF-beta treated HUVECs. The overexpression of AREL1 inhibits the activation of Caspase-3 and Caspase-9 and attenuates cell apoptosis induced by TGF-beta. According to the result of coimmunoprecipitation, AREL1 interacts with the proapoptotic proteins the second mitochondria-derived activator of caspases (SMAC) in TGF-beta treated HUVECs. In addition, miR-320b inhibits the expression of AREL1, and the overexpression of AREL1 attenuates the apoptosis induced by miR-320b mimics in HUVECs. In conclusion, AREL1 is downregulated by miR-320b. AREL1 overexpression inhibits TGF-beta induced apoptosis through downregulating SMAC in vascular endothelial cells. Our study explores pathogenesis regulation mechanism and new biological therapeutic targets for vascular disease.

Automated summary

Abnormal apoptosis of vascular endothelial cells, a key feature of arteriosclerosis, is regulated by the antiapoptotic E3 ubiquitin ligase (AREL1) and miR-320b. TGF-beta treatment downregulates AREL1 expression in HUVECs, leading to increased apoptosis. Overexpression of AREL1 inhibits Caspase-3 and Caspase-9 activation and attenuates apoptosis induced by TGF-beta or miR-320b. Additionally, AREL1 interacts with the proapoptotic protein SMAC in TGF-beta-treated HUVECs. These findings provide insights into the pathogenesis of vascular diseases and suggest new therapeutic targets.