Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1a signaling
Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1a signaling
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DOI：
10.1177/1708538120904297
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发表时间：
2020
期刊：
影响因子：
1.1
通讯作者：
Hong Liu
中科院分区：
文献类型：
--
作者：
Xinhua Wu;Qiuyan Zhao;Zhangrong Chen;Yong-Jian Geng;Wangting Zhang;Qingqing Zhou;Wei Yang;quanyi Liu;Hong Liu
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-1a 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(17b-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-1a mRNA and protein was significantly increased in vascular cells with calcification as compared.to those without calcification (p<0.01). E2 treatment decreased the calcium concentration in vascular cell calcification.and cell calcium nodules in vitro (p<0.05). E2 also lowered the levels of hypoxia-induced factor-1a mRNA and protein.(p<0.01). Oral administration of the hypoxia-induced factor-1a inhibitor dimethyloxetane in castrated rats alleviated.vascular calcification and expression of osteogenesis-related transcription factors, bone morphogenetic protein 2 and.RUNX2 (p<0.01). Finally, bone morphogenetic protein 2 siRNA treatment decreased the levels of p-Smad1/5/8 in A7r5.calcification cells (p<0.01)..Conclusion: Estrogen deficiency enhances vascular calcification. Treatment with estrogen reduces the expression of.hypoxia-induced factor-1a as well as vascular calcification in rats. The estrogen effects occur in a fashion dependent on.hypoxia-induced factor-1a regulation of bone morphogenetic protein-2 and downstream Smad1/5/8.
