Ty-jour t1 - 睡眠呼吸暂停中的钙粘蛋白切割:对间歇性缺氧相关内皮渗透性的新洞察JF - 欧洲呼吸期刊Jo - Eur Respir J Do - 10.1183 / 13993003.04518-2020 SP - 2004518 Au - Harki,Olfa Au - Tamisier,雷尼·奥地比 - 巴尔利,塞巴斯蒂安·奥 - ·萨拉斯·奥尔塔尔,布里奇特·奥 - 萨洛蒙,伊莎贝尔·奥尔格,伊莎贝尔·奥 - 福利 - 富士·弗雷 - 冯···阿布里 - 布朗索 - 布朗森 - 布里亚森 - Briançon-Marjollet,安妮·欧 - Briançon-Marjollet,安妮·奥尔(Briançon-Marjollet),Anne Yu - Briançon-Marjollet,安妮Y1 - 2021 /01/01 UR - //www.qdcxjkg.com/content/early/2021/04/29/13993003.04518-2020.Abstract n2 - 背景阻塞性睡眠呼吸暂停(Osas)导致间歇性缺氧(Ih)反过来诱导内皮功能障碍和动脉粥样硬化进展。我们假设其在血液(SVE)中溶解的释放细胞外片段检测到的Ve-Cadherin切割可能是出苗异常内皮渗透性的早期指标。我们的目的是评估OSAS患者的VE-CADHERIN切割,体内和体外IH模型,以破译细胞机制和后果。从7名健康志愿者的血清暴露于IH,43岁的患者和31例健康对照科目分析了他们的SVE内容。人主动脉内皮细胞(HAEC)在体外暴露于IH的6小时,有或没有HIF-1,酪氨酸激酶或VEGF途径的抗氧化剂或抑制剂。评价VE-CADHERIN裂解和磷酸化,通过测量跨内皮电阻(TEER)和FITC-DEXTRAN FLUX来评估内皮渗透性。结果在治疗前提交给IH和OSAS患者的健康志愿者,血清中显着升高。相反,OSAS患者在连续阳性气道压力处理6个月后减少。OSA是多变量分析中SVE变化的主要因素核算。 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 -