PMID- 19347869
OWN - NLM
STAT- MEDLINE
DCOM- 20090629
LR  - 20161125
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 220
IP  - 2
DP  - 2009 Aug
TI  - Impaired integrin-mediated adhesion contributes to reduced barrier properties in 
      VASP-deficient microvascular endothelium.
PG  - 357-66
LID - 10.1002/jcp.21772 [doi]
AB  - Recent studies point to a significant role of vasodilator-stimulated 
      phosphoprotein (VASP) in the maintenance of endothelial barrier functions in vivo 
      and in vitro. Moreover, it has been reported that VASP is required for activation 
      of the small GTPase Rac 1. However, little is known whether VASP is involved in 
      the regulation of cell adhesion molecules that are critical for maintenance of 
      the endothelial barrier. Here we demonstrate that impaired barrier properties in 
      VASP-deficient (VASP-/-) microvascular myocardial endothelial cells (MyEnd) 
      correlated with both impaired integrin-mediated adhesion as revealed by laser 
      tweezer trapping and reduced integrin-dependent cell migration. This was 
      paralleled by reduction of focal adhesions at the cell periphery as well as of 
      beta(1)-integrin and VE-cadherin cytoskeletal anchorage. Incubation of MyEnd VASP 
      wt with RGD peptide to block interaction of integrins with extracellular matrix 
      (ECM) reduced barrier properties and Rac 1 activity in wt endothelial monolayers 
      mimicking the situation in VASP (-/-) cells under resting conditions. Moreover, 
      cAMP-mediated Rac 1 activation was reduced under conditions of impaired 
      integrin-mediated adhesion in wt cells and cAMP-induced increase in VE-cadherin 
      cytoskeletal anchorage was abolished in VASP (-/-) endothelium. In summary, these 
      data indicate that VASP is required for integrin-mediated adhesion which 
      stabilizes endothelial barrier properties at least in part by facilitating Rac 1 
      activation.
FAU - Schlegel, Nicolas
AU  - Schlegel N
AD  - Institute of Anatomy and Cell Biology, University of Wurzburg, Wurzburg, Germany.
FAU - Waschke, Jens
AU  - Waschke J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Antigens, CD)
RN  - 0 (Cadherins)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Claudin-5)
RN  - 0 (Cldn5 protein, mouse)
RN  - 0 (Detergents)
RN  - 0 (Integrin alpha5beta1)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, mouse)
RN  - 0 (Oligopeptides)
RN  - 0 (Phosphoproteins)
RN  - 0 (cadherin 5)
RN  - 0 (vasodilator-stimulated phosphoprotein)
RN  - 125361-02-6 (Vinculin)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Cadherins/metabolism
MH  - Capillary Permeability/drug effects/*physiology
MH  - Cell Adhesion/*physiology
MH  - Cell Adhesion Molecules/genetics/*metabolism
MH  - Cell Line
MH  - Cell Movement/physiology
MH  - Claudin-5
MH  - Cyclic AMP/metabolism
MH  - Cytoskeleton/metabolism
MH  - Detergents/chemistry
MH  - *Endothelial Cells/cytology/metabolism
MH  - Enzyme Activation
MH  - Integrin alpha5beta1/genetics/*metabolism
MH  - Lasers
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microfilament Proteins/genetics/*metabolism
MH  - *Microvessels/cytology/metabolism
MH  - Occludin
MH  - Oligopeptides/pharmacology
MH  - Phosphoproteins/genetics/*metabolism
MH  - Vinculin/genetics/metabolism
MH  - rac1 GTP-Binding Protein/genetics/metabolism
EDAT- 2009/04/07 09:00
MHDA- 2009/06/30 09:00
CRDT- 2009/04/07 09:00
PHST- 2009/04/07 09:00 [entrez]
PHST- 2009/04/07 09:00 [pubmed]
PHST- 2009/06/30 09:00 [medline]
AID - 10.1002/jcp.21772 [doi]
PST - ppublish
SO  - J Cell Physiol. 2009 Aug;220(2):357-66. doi: 10.1002/jcp.21772.