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Matrix‐specific PAK activation regulates vascular permeability in atherosclerosis
Author(s) -
Orr A. Wayne,
Stockton Rebecca,
Simmers Michael,
Sanders John M.,
Blackman Brett R.,
Schwartz Martin A.
Publication year - 2007
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.21.5.a268-d
Subject(s) - fibronectin , microbiology and biotechnology , basement membrane , permeability (electromagnetism) , vascular permeability , endothelium , in vivo , chemistry , phosphorylation , endothelial stem cell , endothelial activation , biology , in vitro , endocrinology , extracellular matrix , membrane , biochemistry
Elevated permeability of the endothelium is thought to be crucial in atherogenesis because it allows circulating LDL to access subendothelial monocytes. Both local hemodynamics and cytokines may govern endothelial permeability in atherosclerotic plaque. We recently found that p21 activated kinase (PAK) regulates endothelial permeability. We now report that onset of fluid flow, atherogenic flow, oxidized LDL and pro‐atherosclerotic cytokines all stimulate PAK phosphorylation and recruitment to cell‐cell junctions. Activation of PAK is higher in cells plated on fibronectin compared to basement membrane proteins. In vivo, PAK is activated in atherosclerosis‐prone regions of arteries, and correlates with fibronectin in the subendothelium. Inhibiting PAK in vivo reduces permeability in atherosclerosis‐prone regions. Matrix‐specific PAK activation therefore mediates elevated vascular permeability in atherosclerosis.