MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism

Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs). Overactivation of IGF signaling has been implicated in promoting the aging process. Lectinlike oxidized lowdensity lipoprotein (oxLDL) receptor1 (LOX1) is a scavenger receptor that mediates the internalization of oxLDL into cells. Previous studies by our group have indicated that microRNA let7g exerts an antiaging effect on ECs and also suppresses LOX-1 expression. Since LOX1 also induces the aging process, the present study we explored whether let7g still exerts an antiaging effect on ECs when LOX1 is suppressed. Angiotensin II (Ang II) was used to induce senescence in ECs. It was revealed that Ang II significantly increased the expression of aging markers, including βgalactosidase, LOX1, IGF1 and its receptor IGF1R. On the contrary, Ang II decreased the expression of the antiaging gene sirtuin 1 (SIRT1). When LOX1 was knocked down by small interfering RNA, let7g still dosedependently decreased the expression of βgalactosidase (βgal), LOX1, IGF1 and IGF1R, and SIRT1 was still upregulated. Using senescenceassociated βgal staining, it was confirmed that let7g exerts a LOX1independent antiaging effect on ECs. In conclusion, the present study demonstrated that let7g has an antiaging effect regardless of the presence or absence of LOX-1.