Activation of the stress protein response prevents the development of pulmonary edema by inhibiting VEGF cell signaling in a model of lung ischemia-reperfusion injury in rats

Micaela Godzich, M. Hodnett, J. A. Frank, G. Su, M. Pespeni, A. Angel, M. B. Howard, M. A. Matthay, J. F. Pittet

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Lung endothelial damage is a characteristic morphological feature of ischemia-reperfusion (I/R) injury, although the molecular steps involved in the loss of endothelial integrity are still poorly understood. We tested the hypothesis that the activation of vascular endothelial growth factor (VEGF) cell signaling would be responsible for the increase in lung vascular permeability seen early after the onset of I/R in rats. Furthermore, we hypothesized that the I/R-induced pulmonary edema would be significantly attenuated in rats by the activation of the stress protein response. Pretreatment with Ad Flk-1, an adenovirus encoding for the soluble VEGF receptor type II, prevented I/R-mediated increase in lung vascular permeability in rats. Furthermore, the I/R-induced lung injury was significantly decreased by prior activation of the stress protein response with geldanamycin or pyrrolidine dithiocarbamate. In vitro studies demonstrated that VEGF caused an increase in protein permeability across primary cultures of bovine macro- and microvascular lung endothelial cell monolayers that were associated with a phosphorylation of VE- and E-cadherin and the formation of actin stress fibers. Activation of the stress protein response prevented the VEGF-mediated changes in protein permeability across these cell monolayers and reduced the phosphorylation of VE-and E-cadherins, as well as the formation of actin stress fibers in these cells.

Original languageEnglish (US)
JournalFASEB Journal
Volume20
Issue number9
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

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Cell signaling
vascular endothelial growth factors
Pulmonary Edema
ischemia
Heat-Shock Proteins
Reperfusion Injury
edema
Vascular Endothelial Growth Factor A
Reperfusion
Rats
Ischemia
Chemical activation
lungs
Lung
Stress Fibers
Phosphorylation
rats
permeability
Capillary Permeability
Cadherins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Activation of the stress protein response prevents the development of pulmonary edema by inhibiting VEGF cell signaling in a model of lung ischemia-reperfusion injury in rats. / Godzich, Micaela; Hodnett, M.; Frank, J. A.; Su, G.; Pespeni, M.; Angel, A.; Howard, M. B.; Matthay, M. A.; Pittet, J. F.

In: FASEB Journal, Vol. 20, No. 9, 01.07.2006.

Research output: Contribution to journalArticle

Godzich, Micaela ; Hodnett, M. ; Frank, J. A. ; Su, G. ; Pespeni, M. ; Angel, A. ; Howard, M. B. ; Matthay, M. A. ; Pittet, J. F. / Activation of the stress protein response prevents the development of pulmonary edema by inhibiting VEGF cell signaling in a model of lung ischemia-reperfusion injury in rats. In: FASEB Journal. 2006 ; Vol. 20, No. 9.
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