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

• Published in: Molecular and cellular endocrinology Vol. 580; p. 112111
• Main Authors: Lv, Yifei, Huang, Yizhou, Fan, Huiyu, Zhao, Yunxiu, Ma, Linjuan, Lan, Yibing, Li, Chunming, Chen, Peiqiong, Lou, Zheng, Zhou, Jianhong
• Format: Journal Article
• Language: English
• Published: Ireland 15.01.2024
• Subjects: Apoptosis; Estradiol - metabolism; Estradiol - pharmacology; Estrogens - metabolism; Female; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - toxicity; Transforming Growth Factor beta - metabolism; TGF-β; Senescence; 17β-estradiol; THBS1; Apoptosis
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2023.112111

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