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Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2003 Oct; Vol. 285 (4), pp. L785-97. Date of Electronic Publication: 2003 Mar 14. - Publication Year :
- 2003
-
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 microM). 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.
- Subjects :
- Cell Survival physiology
Cells, Cultured
Conditioning, Psychological physiology
Cytoskeleton physiology
Electric Impedance
Endothelium, Vascular drug effects
Endothelium, Vascular metabolism
Endothelium, Vascular physiology
Gap Junctions physiology
Gene Expression Profiling
Humans
Myosin Light Chains metabolism
Oligonucleotide Array Sequence Analysis
Periodicity
Phosphorylation drug effects
Pulmonary Artery drug effects
Pulmonary Artery metabolism
Stress, Mechanical
Thrombin pharmacology
Time Factors
Capillary Permeability physiology
Pulmonary Artery physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 285
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12639843
- Full Text :
- https://doi.org/10.1152/ajplung.00336.2002