title: Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II.
abstract: Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P< 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement.
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Zhiyong
authors.identifier: 0000-0001-6281-5668
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Feifeng
authors.initials: F
authors.lastname: Dai
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Huagang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002199:Capillary Permeability; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D008875:Middle Aged; D009154:Mutation; D010539:Permeability; D010766:Phosphorylation; D051381:Rats; D000099152:Cadherin 5
chemical_list: D000804:Angiotensin II; D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5