Diverse effects of vascular endothelial growth factor on human pulmonary endothelial barrier and migration

T. Mirzapoiazova, I. Kolosova, P. V. Usatyuk, V. Natarajan, Alexander Dmitriyevich Verin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Increased endothelial permeability is involved in the pathogenesis of many cardiovascular and pulmonary diseases. Vascular endothelial growth factor (VEGF) is a permeability-increasing cytokine. At the same time, VEGF is known to have a beneficial effect on endothelial cells (EC), increasing their survival. Pulmonary endothelium, particularly, may be exposed to higher VEGF concentrations, since the VEGF level is the higher in the lungs than in any other organ. The purpose of this work was to evaluate the effects of VEGF on barrier function and motility of cultured human pulmonary EC. Using transendothelial resistance measurements as an indicator of permeability, we found that 10 ng/ml VEGF significantly improved barrier properties of cultured human pulmonary artery EC (118.6 ± 0.6% compared with 100% control, P < 0.001). In contrast, challenge with 100 ng/ml VEGF decreased endothelial barrier (71.6 ± 1.0% compared with 100% control, P < 0.001) and caused disruption of adherens junctions. VEGF at both concentrations increased cellular migration; however, 10 ng/ml VEGF had a significantly stronger effect. VEGF caused a dose-dependent increase in intracellular Ca2+ concentration; however, phosphorylation of myosin light chain was detectably elevated only after treatment with 100 ng/ml. In contrast, 10 ng/ml but not 100 ng/ml VEGF caused a significant increase in intracellular cAMP (known barrier-protective stimulus) compared with nonstimulated cells (1,096 ± 157 and 610 ± 86 fmol/mg, respectively; P < 0.024). Y 576-specific phosphorylation of focal adhesion kinase was also stimulated by 10 ng/ml VEGF. Our data suggest that, depending on its concentration, VEGF may cause diverse effects on pulmonary endothelial permeability via different signaling pathways.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number4
DOIs
StatePublished - Oct 9 2006
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Lung
Permeability
Endothelial Cells
human VEGFA protein
Phosphorylation
Adherens Junctions
Focal Adhesion Protein-Tyrosine Kinases
Myosin Light Chains
Pulmonary Artery
Lung Diseases
Endothelium
Cardiovascular Diseases
Cytokines

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Diverse effects of vascular endothelial growth factor on human pulmonary endothelial barrier and migration. / Mirzapoiazova, T.; Kolosova, I.; Usatyuk, P. V.; Natarajan, V.; Verin, Alexander Dmitriyevich.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 4, 09.10.2006.

Research output: Contribution to journalArticle

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