Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch

Konstantin G. Birukov, Jeffrey R. Jacobson, Alejandro A. Flores, Shui Q. Ye, Anna A. Birukova, Alexander D. Verin, Joe GN Garcia

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Ventilator-induced lung injury syndromes are characterized by profound increases in vascular leakiness and activation of inflammatory processes. To explore whether excessive cyclic stretch (CS) directly causes vascular barrier disruption or enhances endothelial cell sensitivity to edemagenic agents, human pulmonary artery endothelial cells (HPAEC) were exposed to physiologically (5% elongation) or pathologically (18% elongation) relevant levels of strain. CS produced rapid (10 min) increases in myosin light chain (MLC) phosphorylation, activation of p38 and extracellular signal-related kinase 1/2 MAP kinases, and actomyosin remodeling. Acute (15 min) and chronic (48 h) CS markedly enhanced thrombin-induced MLC phosphorylation (2.1-fold and 3.2-fold for 15-min CS at 5 and 18% elongation and 2.1-fold and 3.1-fold for 48-h CS at 5 and 18% elongation, respectively). HPAEC preconditioned at 18% CS, but not at 5% CS, exhibited significantly enhanced thrombin-induced reduction in transendothelial electrical resistance but did not affect barrier protective effect of sphingosine-1-phosphate (0.5 μM). Finally, expression profiling analysis revealed a number of genes, including small GTPase rho, apoptosis mediator ZIP kinase, and proteinase activated receptor-2, to be regulated by CS in an amplitude-dependent manner. Thus our study demonstrates a critical role for the magnitude of CS in regulation of agonist-mediated pulmonary endothelial cell permeability and strongly suggests phenotypic regulation of HPAEC barrier properties by CS.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number4 29-4
StatePublished - Oct 1 2003
Externally publishedYes

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Endothelial Cells
Lung
Pulmonary Artery
Myosin Light Chains
Thrombin
Blood Vessels
Death-Associated Protein Kinases
MAP Kinase Kinase 2
Ventilator-Induced Lung Injury
MAP Kinase Kinase 1
Phosphorylation
PAR-2 Receptor
Actomyosin
Monomeric GTP-Binding Proteins
Electric Impedance
Permeability
Apoptosis
Genes

Keywords

  • Actin
  • Cytoskeleton
  • Mechanical strain
  • Myosin
  • Permeability
  • Phosphorylation
  • Thrombin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch. / Birukov, Konstantin G.; Jacobson, Jeffrey R.; Flores, Alejandro A.; Ye, Shui Q.; Birukova, Anna A.; Verin, Alexander D.; Garcia, Joe GN.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 285, No. 4 29-4, 01.10.2003.

Research output: Contribution to journalArticle

Birukov, Konstantin G. ; Jacobson, Jeffrey R. ; Flores, Alejandro A. ; Ye, Shui Q. ; Birukova, Anna A. ; Verin, Alexander D. ; Garcia, Joe GN. / Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2003 ; Vol. 285, No. 4 29-4.
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