Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling

• Published in: Vascular 2020-08, Vol.28 (4), p.465-474
• Main Authors: Wu, Xinhua, Zhao, Qiuyan, Chen, Zhangrong, Geng, Yong-Jian, Zhang, Wanting, Zhou, Qingqing, Yang, Wei, Liu, Quanyi, Liu, Hong
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1708-5381; 1708-539X
• DOI: 10.1177/1708538120904297

Objective Calcification serves as a surrogate for atherosclerosis-associated vascular diseases, and coronary artery calcification is mediated by multiple pathogenic factors. Estrogen is a known factor that protects the arterial wall against atherosclerosis, but its role in the coronary artery calcification development remains largely unclear. This study tested the hypothesis that estrogen inhibits coronary artery calcification via the hypoxia-induced factor-1α pathway. Methods Eight-week-old healthy female Sprague–Dawley rats were castrated, and vitamin D3 was administered orally to establish. Hypoxia-induced factor-1 inhibitor was administered to test its effect on vascular calcification and expression of bone morphogenetic protein 2 and runt-related transcription factor-2. Vascular smooth muscle cell calcification was induced with CaCl2 in rat aortic smooth muscle cells in the presence or absence of E2(17β-estradiol) and bone morphogenetic protein 2 siRNA intervention. Results The estrogen levels in ovariectomized rats were significantly decreased, as determined by ELISA. Expression of hypoxia-induced factor-1α mRNA and protein was significantly increased in vascular cells with calcification as compared to those without calcification (p