TY - JOUR T1 - VE-Cadherin切割与睡眠呼吸暂停:洞察间歇hypoxia-related内皮渗透性JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.04518 -2020欧元SP - 2004518 AU Harki Olfa盟——Tamisier Renaud盟——Pepin jean - louis AU -贝利Sebastien盟——Mahmani Anissa盟——Gonthier林盟-所罗门,这是盟——Vilgrain伊莎贝尔盟——Faury Gilles盟——Briancon-Marjollet安妮Y1 - 2021/01/01 UR - //www.qdcxjkg.com/content/early/2021/04/29/13993003.04518 - 2020. -抽象N2 -背景阻塞性睡眠呼吸暂停(群)导致间歇性缺氧(IH),进而诱发内皮功能障碍和动脉粥样硬化进展。我们假设VE-Cadherin切割，通过其释放的在血液中溶解的细胞外片段(sVE)检测到，可能是紧急异常内皮通透性的早期指标。我们的目的是评估VE-cadherin切割在osa患者和体内和体外IH模型中，以破译细胞机制和后果。方法对7名健康志愿者、43名OSAS患者和31名健康对照者的血清sVE含量进行分析。人主动脉内皮细胞(HAEC)暴露于体外6小时IH，有或没有HIF-1、酪氨酸激酶或VEGF途径的抗氧化剂或抑制剂。评估VE-Cadherin切割和磷酸化，通过测量跨内皮电阻(TEER)和fitc -右旋糖酐通量评估内皮通透性。结果治疗前接受IH和osaas治疗的健康志愿者血清sVE明显升高，而持续气道正压治疗6个月后OSAS患者血清sVE降低。在多变量分析中，OSAS是导致sVE变异的主要因素。 In in vitro experiments, cleavage and expression of VE-Cadherin increased upon HAEC exposure to IH. TEER decreased and FITC-Dextran flux increased. These effects were reversed by all the pharmacological inhibitors tested.Conclusion We suggest that in OSAS, IH increases endothelial permeability in OSAS by inducing VE-Cadherin cleavage through ROS production and activation of HIF-1, VEGF and tyrosine kinase pathways.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Harki has nothing to disclose.Conflict of interest: Dr. Tamisier reports grants, personal fees and other from Agiradom (Healthcare provider), grants and personal fees from Resmed, grants from Inspire, grants from Navigant, grants from Jazz pharmaceuticals, personal fees from Elivie, personal fees from Philips, outside the submitted work; .Conflict of interest: Dr. Pépin reports grants from Air Liquide Foundation, grants and personal fees from Agiradom, grants and personal fees from AstraZeneca, grants from Fisher and Paykel, grants from Mutualia, grants and personal fees from Philips, grants and personal fees from Resmed, grants from Vitalaire,, grants from Boehringer Ingelheim, grants from Jazz Pharmaceuticals, grants from Night Balance, grants from Sefam, all outside the submitted work; .Conflict of interest: Dr. Bailly has nothing to disclose.Conflict of interest: Dr. Mahmani has nothing to disclose.Conflict of interest: Dr. Gonthier has nothing to disclose.Conflict of interest: Dr. Salomon has nothing to disclose.Conflict of interest: Dr. Vilgrain has nothing to disclose.Conflict of interest: Dr. Faury has nothing to disclose.Conflict of interest: Dr. Briançon-Marjollet has nothing to disclose. ER -