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PECAM‐1 and VEGF‐Dependent Permeability
Author(s) -
Abraham Valsamma,
Zoga Kristi,
Desai Mitan,
Massa Alyssa,
DeLisser Horace
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08648
Subject(s) - vascular endothelial growth factor , vascular permeability , enos , vascular endothelial growth factor a , medicine , in vivo , endocrinology , protein kinase b , phosphorylation , microbiology and biotechnology , biology , chemistry , immunology , vegf receptors , nitric oxide , genetics , nitric oxide synthase
VEGF has long been recognized as a potent permeability factor and PECAM‐1 has been implicated in endothelial barrier function. However, the role of PECAM‐1 in VEGF‐mediated permeability is unclear. We observed in studies of wild type and PECAM‐1‐null mice that the loss of PECAM‐1 was not associated with an increase in the baseline permeability of non‐stimulated vessels. Consistent with this was the finding that the junctional architecture of quiescent vessels was preserved in the PECAM‐1‐deficient mice. In contrast, VEGF‐dependent permeability was significantly impaired in the skin of PECAM‐1‐null mice compared to wild type animals, while the dermal responses to two other factors (PAF and histamine) were preserved in the mutant mice. In line with these in vivo findings, i n vitro permeability induced by VEGF (but not that of PAF) was reduced in PECAM‐1‐null endothelial cells (ECs). Further, VEGF receptor phosphorylation and downstream activation of PI3 kinase, Akt and eNOS following VEGF stimulation were blunted in PECAM‐1‐null ECs. Together these data implicate the involvement of PECAM‐1 in VEGF‐mediated permeability. Support or Funding Information Competitive Pilot Project Fund, VA Health Network VISN4