H2O2 downregulate SIRT7`s protective role of endothelial premature dysfunction via microRNA-335-5p
Endothelial senescence is believed to constitute the initial pathogenesis of the atherosclerotic cardiovascular disease (ASCVD). MicroRNA-335-5p (miR-335-5p) expression is significantly upregulated in oxidative stress-induced endothelial cells (ECs). Sirtuin7 (SIRT7) is considered to prevent EC senescence, yet data on its response to ASCVD risk factors are limited. This study analyzed the elevated levels of miR-335-5p and the decreased levels of SIRT7 in human umbilical vein endothelial cells (HUVECs) , and found that high glucose, tumour necrosis factor-α (TNF-α), and H2O2 are the three contributing factors that induced cellular senescence. The current study also assessed premature endothelial senescence and decreased proliferation, adhesion, migration, and nitric oxide secretion in HUVECs with these risk factors together with SIRT7-siRNA transfection. It found that the miR-335-5p inhibitor attenuated the downregulation of SIRT7 expression induced by oxidative stress in HUVECs, and SIRT7 overexpression exerts a rescue effect against miR-335-5p induced endothelial dysfunction. Furthermore, the direct binding of miR-335-5p to SIRT7 was observed in HEK-293T. Therefore, it can be inferred that miR-335-5p downregulates the expression of SIRT7 in human cells. Current findings may provide deeper insights into the underlying mechanisms of endothelial senescence and potential therapeutic targets of ASCVD as well as other age-related diseases.