17β-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-β/ Smad axis

Before menopause, females exhibit a lower incidence of cardiovascular disease than age-matched males, possibly owing to the protective effects of sex hormones. 17 beta-estradiol (17 beta-E2) protects against oxidative stress-induced injury by suppressing thrombospondin-1 (THBS1) expression in endothelial cells. Here, we examined the role of 17 beta-E2-mediated THBS1 suppression in preventing cell senescence and apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultivated and treated with siRNA or overexpression plasmids to regulate THBS1. H2O2, estrogen-activity modulating drugs, and LY2109761 (a TGF-beta kinase inhibitor) treatments were applied. THBS1 knockdown repressed, and its overexpression aggravated, H2O2-induced cell injury, affecting cell death, proliferation, senescence, and apoptosis. 17 beta-E2 inhibited THBS1 mRNA and protein expression time- and dose-dependently, by targeting ER beta. THBS1 overexpression blocked 17 beta-E2 from preventing H2O2-induced injury, significantly activating the TGF-beta/Smad pathway. 17 beta-E2 inhibited H2O2-induced oxidative stress by downregulating THBS1 expression and TGF-beta/Smad signaling in HUVECs. The THBS1/TGF-beta/Smad axis could thus be a therapeutic target.

Automated summary

Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.