Show simple item record

dc.contributor.authorManiatis, Nikolaos A.
dc.contributor.authorKardara, Matina
dc.contributor.authorHecimovich, Dan
dc.contributor.authorLetsiou, Eleftheria
dc.contributor.authorCastellon, Maricela
dc.contributor.authorRoussos, Charalambos
dc.contributor.authorShinin, Vasily
dc.contributor.authorVotta‑Vellis, E. Gina
dc.contributor.authorSchwartz, David E.
dc.contributor.authorMinshall, Richard D.
dc.date.accessioned2013-12-06T16:07:24Z
dc.date.available2013-12-06T16:07:24Z
dc.date.issued2012-10
dc.identifier.bibliographicCitationManiatis NA, Kardara M, Hecimovich D, Letsiou E, Castellon M, Roussos C, Shinin V, Votta-Vellis EG, Schwartz DE, Minshall RD. Role of caveolin-1 expression in the pathogenesis of pulmonary edema in ventilator-induced lung injury. Pulmonary Circulation. 2012 Oct;2(4):452-60. doi: 10.4103/2045-8932.105033.en_US
dc.identifier.issn2045-8932
dc.identifier.urihttp://hdl.handle.net/10027/10845
dc.description© 2012 by Medknow Publications, Pulmonary Circulationen_US
dc.description.abstractCaveolin-1 is a key regulator of pulmonary endothelial barrier function. Here, we tested the hypothesis that caveolin-1 expression is required for ventilator-induced lung injury (VILI). Caveolin-1 gene-disrupted (Cav-1(-/-)) and age-, sex-, and strain-matched wild-type (WT) control mice were ventilated using two protocols: volume-controlled with protective (8 mL/kg) versus injurious (21 mL/Kg) tidal volume for up to 6 hours; and pressure-controlled with protective (airway pressure = 12 cm H(2)O) versus injurious (30 cm H(2)O) ventilation to induce lung injury. Lung microvascular permeability (whole-lung (125)I-albumin accumulation, lung capillary filtration coefficient [K(f, c)]) and inflammatory markers (bronchoalveolar lavage [BAL] cytokine levels and neutrophil counts) were measured. We also evaluated histologic sections from lungs, and the time course of Src kinase activation and caveolin-1 phosphorylation. VILI induced a 1.7-fold increase in lung (125)I-albumin accumulation, fourfold increase in K(f, c), significantly increased levels of cytokines CXCL1 and interleukin-6, and promoted BAL neutrophilia in WT mice. Lung injury by these criteria was significantly reduced in Cav-1(-/-) mice but fully restored by i.v. injection of liposome/Cav-1 cDNA complexes that rescued expression of Cav-1 in lung microvessels. As thrombin is known to play a significant role in mediating stretch-induced vascular injury, we observed in cultured mouse lung microvascular endothelial cells (MLECs) thrombin-induced albumin hyperpermeability and phosphorylation of p44/42 MAP kinase in WT but not in Cav-1(-/-) MLECs. Thus, caveolin-1 expression is required for mechanical stretch-induced lung inflammation and endothelial hyperpermeability in vitro and in vivo.en_US
dc.description.sponsorshipThis work was supported by NIH R01 HL71626 and P01 HL60678 (RDM), and American Thoracic Society/Acute Respiratory Distress Syndrome Foundation/Sepsis Alliance Partnership Research Grant (NAM).en_US
dc.language.isoen_USen_US
dc.publisherMedknow Publicationsen_US
dc.subjectthrombinen_US
dc.subjectcaveolaeen_US
dc.subjectlung inflammationen_US
dc.titleRole of caveolin‑1 expression in the pathogenesis of pulmonary edema in ventilator‑induced lung injuryen_US
dc.typeArticleen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record