机构：[1]Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.[2]Department of Respiratory Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 West Xianxia Road, Shanghai, 200335, China.[3]Department of Respiratory Medicine, Huashan Hospital, Fudan University School of Medicine, No.12 Middle, Urumqi Road, Shanghai, 200040, China.[4]Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, No. 600 Yishan Road, Shanghai, 200233, China.
Chronic intermittent hypoxia (IH) contributes to obstructive sleep apnea (OSA)-related cardiovascular diseases through increasing oxidative stress. It has been widely recognized that estradiol decreases the risk for cardiovascular disease, but the estrogen replacement therapy is limited for its side effects. Thioredoxin (Trx) and its endogenous inhibitor, thioredoxin-interacting protein (Txnip), are associated with the protective effect of estradiol in some conditions. In this study, we aimed to explore whether estradiol could protect against IH-induced vascular injury, and the possible effect of Trx-1/Txnip in this process. Forty-eight adult female C57/BL6J mice were randomly divided into 4 groups, ovariectomy combined with IH group, sham operation combined with IH group, IH group and the control group. The mice treated with IH for 8 hrs/day, and 28 days. IH induced the injury of aorta, and ovariectomized mice were more prone to the IH-induced aortic injury, with higher level of oxidative stress. In vitro, estradiol increased Trx-1 level, but decreased the level of Txnip and oxidative stress in human umbilical vein endothelial cells (HUVECs) treated with IH for 16 hrs. Knock-down of Txnip by specific siRNA rescued oxidative stress and apoptosis. In conclusion, estradiol protects against IH-induced vascular injury, partially through the regulation of Trx-1/Txnip pathway.
基金：
National Natural Science Foundation of China (NSFC) [81070068, 81270148, 81570082]
第一作者机构：[1]Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.[2]Department of Respiratory Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 West Xianxia Road, Shanghai, 200335, China.
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推荐引用方式(GB/T 7714)：
Lan Xiao Fei,Zhang Xiu Juan,Lin Ying Ni,et al.Estradiol Regulates Txnip and Prevents Intermittent Hypoxia-Induced Vascular Injury[J].SCIENTIFIC REPORTS.2017,7:doi:10.1038/s41598-017-10442-7.
