Focal adhesion kinase mediates porcine venular hyperpermeability elicited by vascular endothelial growth factor

J Physiol. 2003 Nov 1;552(Pt 3):691-9. doi: 10.1113/jphysiol.2003.048405. Epub 2003 Aug 29.

Abstract

Focal adhesion kinase (FAK) is known to mediate endothelial cell adhesion and migration in response to vascular endothelial growth factor (VEGF). The aim of this study was to explore a potential role for FAK in VEGF regulation of microvascular endothelial barrier function. The apparent permeability coefficient of albumin (Pa) was measured in intact isolated porcine coronary venules. Treating the vessels with VEGF induced a time- and concentration-dependent increase in Pa. Inhibition of FAK through direct delivery of FAK-related non-kinase (FRNK) into venular endothelium did not alter basal barrier function but significantly attenuated VEGF-elicited hyperpermeability. Furthermore, cultured human umbilical vein endothelial monolayers displayed a similar hyperpermeability response to VEGF which was greatly attenuated by FRNK. Western blot analysis showed that VEGF promoted FAK phosphorylation in a time course correlating with that of venular hyperpermeability. The phosphorylation response was blocked by FRNK treatment. In addition, VEGF stimulation caused a significant morphological change of FAK from a punctate pattern to an elongated, dash-like staining that aligned with the longitudinal axis of the cells. Taken together, the results suggest that FAK contributes to VEGF-elicited vascular hyperpermeability. Phosphorylation of FAK may play an important role in the signal transduction of vascular barrier response to VEGF.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology*
  • Cells, Cultured
  • Coronary Circulation
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • Protein-Tyrosine Kinases / pharmacology
  • Protein-Tyrosine Kinases / physiology*
  • Serum Albumin, Bovine / pharmacokinetics
  • Signal Transduction / physiology
  • Swine
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A / administration & dosage
  • Vascular Endothelial Growth Factor A / physiology*
  • Venules / metabolism*

Substances

  • Vascular Endothelial Growth Factor A
  • Serum Albumin, Bovine
  • FAK-related nonkinase
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human