机构：[1]Department of Cardiology, First Affiliated Hospital of Dali University, Dali, Yunnan, China.[2]Yunnan Trans-plateau Cardiovascular Disease of Prevention and Treatment Research Center, Yunnan, China.[3]Institute of Trans-plateau Cardiovascular Disease Prevention and Treatment of Dali University, Dali, Yunnan, China.[4]Department of Internal Medicine, The Center for Cardiovascular Biology and Atherosclerosis, McGovern School of Medicine, University of Texas Health Science Center at Houston, TX, USA.
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.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.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 < 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-1α mRNA and protein (p < 0.01). Oral administration of the hypoxia-induced factor-1α 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).Estrogen deficiency enhances vascular calcification. Treatment with estrogen reduces the expression of hypoxia-induced factor-1α as well as vascular calcification in rats. The estrogen effects occur in a fashion dependent on hypoxia-induced factor-1α regulation of bone morphogenetic protein-2 and downstream Smad1/5/8.
基金：
The study was funded by the National Nature Science
Foundation of China (No. 81560073).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|4 区医学
小类|4 区外周血管病
最新[2023]版：
大类|4 区医学
小类|4 区外周血管病
第一作者：
第一作者机构：[1]Department of Cardiology, First Affiliated Hospital of Dali University, Dali, Yunnan, China.[2]Yunnan Trans-plateau Cardiovascular Disease of Prevention and Treatment Research Center, Yunnan, China.[3]Institute of Trans-plateau Cardiovascular Disease Prevention and Treatment of Dali University, Dali, Yunnan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Cardiology, First Affiliated Hospital of Dali University, Dali, Yunnan, China.[2]Yunnan Trans-plateau Cardiovascular Disease of Prevention and Treatment Research Center, Yunnan, China.[3]Institute of Trans-plateau Cardiovascular Disease Prevention and Treatment of Dali University, Dali, Yunnan, China.[*1]Department of Cardiology, First Affiliated Hospital of Dali University, No. 32 Jiashibo Avenue, Dali 671000, Yunnan Province, China.
推荐引用方式(GB/T 7714)：
Wu Xinhua,Zhao Qiuyan,Chen Zhangrong,et al.Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling[J].Vascular.2020,28(4):465-474.doi:10.1177/1708538120904297.
APA：
Wu Xinhua,Zhao Qiuyan,Chen Zhangrong,Geng Yong-Jian,Zhang Wanting...&Liu Hong.(2020).Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling.Vascular,28,(4)
MLA：
Wu Xinhua,et al."Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling".Vascular 28..4(2020):465-474
