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.

Blood pressure profile of postmenopausal women with OSAHS was affected by both BMI and AHI. But those of premenopausal ones were predominantly related to BMI.

PurposeChronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic 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.MethodsHUVECs 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.ResultsA 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.ConclusionThe ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.