Purpose: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the antiapoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure. Methods: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting. Results: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downstream target, cellular inhibitor of apoptosis protein 1 (c-IAP1), were up-regulated by E2. We also observed that E2 decreased the level of cleaved caspase-3 and inhibited cell apoptosis in IH-exposed HUVECs. The inhibition of ATM abolished the anti-apoptotic effect of E2. Conclusion: The ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81700084, 81070068, 81770084, 81570082, 81700085]; Shanghai Key Discipline for Respiratory Disease [2017ZZ02014]; Key Research Program of Shanghai Science and Technology Commission [18140903600]
第一作者机构：[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Resp & Crit Care Med, Sch Med, Shanghai 200025, Peoples R China[2]Shanghai Jiao Tong Univ, Inst Resp Dis, Sch Med, Shanghai 200025, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Resp & Crit Care Med, Sch Med, Shanghai 200025, Peoples R China[2]Shanghai Jiao Tong Univ, Inst Resp Dis, Sch Med, Shanghai 200025, Peoples R China[*1]Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
推荐引用方式(GB/T 7714)：
Lin Ying Ni,Lan Xiao Fei,Liu Zhuo Ran,et al.Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia[J].NATURE AND SCIENCE OF SLEEP.2019,11:357-366.doi:10.2147/NSS.S231456.
APA：
Lin, Ying Ni,Lan, Xiao Fei,Liu, Zhuo Ran,Yan, Ya Ru,Zhou, Jian Ping...&Li, Qing Yun.(2019).Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia.NATURE AND SCIENCE OF SLEEP,11,
MLA：
Lin, Ying Ni,et al."Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia".NATURE AND SCIENCE OF SLEEP 11.(2019):357-366
