title: Cardiopulmonary bypass increases pulmonary microvascular permeability through the Src kinase pathway: Involvement of caveolin-1 and vascular endothelial cadherin.
abstract: Changes in pulmonary microvascular permeability following cardiopulmonary bypass (CPB) and the underlying mechanisms have not yet been established. Therefore, the aim of the present study was to elucidate the alterations in pulmonary microvascular permeability following CPB and the underlying mechanism. The pulmonary microvascular permeability was measured using Evans Blue dye (EBD) exclusion, and the neutrophil infiltration and proinflammatory cytokine secretion was investigated. In addition, the activation of Src kinase and the phosphorylation of caveolin‑1 and vascular endothelial cadherin (VE‑cadherin) was examined. The results revealed that CPB increased pulmonary microvascular leakage, neutrophil count and proinflammatory cytokines in the bronchoalveolar lavage fluid, and activated Src kinase. The administration of PP2, an inhibitor of Src kinase, decreased the activation of Src kinase and attenuated the increase in pulmonary microvascular permeability observed following CPB. Two important proteins associated with vascular permeability, caveolin‑1 and VE‑cadherin, were significantly activated at 24 h in the lung tissues following CPB, which correlated with the alterations in pulmonary microvascular permeability and Src kinase. PP2 administration inhibited their activation, suggesting that they are downstream factors of Src kinase activation. The data indicated that the Src kinase pathway increased pulmonary microvascular permeability following CPB, and the activation of caveolin‑1 and VE‑cadherin may be involved. Inhibition of this pathway may provide a potential therapy for acute lung injury following cardiac surgery.
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors: Junwen
authors: J
authors: Zhang
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors: Zhaolei
authors: Z
authors: Jiang
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors: Chunrong
authors: C
authors: Bao
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors: Ju
authors: J
authors: Mei
authors: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors: Jiaquan
authors: J
authors: Zhu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass; D051242:Caveolin 1 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000378:metabolism; D020556:Neutrophil Infiltration; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017207:Rats, Sprague-Dawley; D019061:src-Family Kinases / Q000502:physiology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051242:Caveolin 1; D016207:Cytokines; D019061:src-Family Kinases; D000099152:Cadherin 5