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

Abstract

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. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a scavenger receptor that mediates the internalization of oxLDL into cells. Previous studies by our group have indicated that microRNA let-7g exerts an anti-aging effect on ECs and also suppresses LOX-1 expression. Since LOX-1 also induces the aging process, the present study we explored whether let-7g still exerts an anti-aging effect on ECs when LOX-1 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 β-galactosidase, LOX-1, IGF1 and its receptor IGF1R. On the contrary, Ang II decreased the expression of the anti-aging gene sirtuin 1 (SIRT1). When LOX-1 was knocked down by small interfering RNA, let-7g still dose-dependently decreased the expression of β-galactosidase (β-gal), LOX-1, IGF1 and IGF1R, and SIRT1 was still upregulated. Using senescence-associated β-gal staining, it was confirmed that let-7g exerts a LOX-1-independent anti-aging effect on ECs. In conclusion, the present study demonstrated that let-7g has an anti-aging effect regardless of the presence or absence of LOX-1.