PAR-2 mediates increased inflammatory cell adhesion and neointima formation following vascular injury in the mouse.
Activation of PAR-2 in the vasculature affects vascular tone and adhesion of leukocytes to the endothelium. Since adhesion of leukocytes is increased following vascular injury and is important in determining the extent of neointima formation, we hypothesised that mice lacking PAR-2 may have reduced neointima formation following vascular injury. PAR-2 activating peptides and trypsin induced endothelium-dependent relaxation of mouse carotid artery which was absent in the knockout mouse. Lack of a PAR-2 receptor did not affect lymphocyte adhesion under basal conditions, but reduced the contractile response produced by lymphocytes. Twenty-eight days after denuding injury, vessel contraction to lymphocytes was reduced in both strains while lymphocyte adhesion was significantly greater in PAR-2(+/+) mice compared to the PAR-2 knockout mice. Neointimal area was markedly reduced in the PAR-2 knockout mouse. Our data show that PAR-2 modulates inflammatory cell adhesion when stimulated and in mice lacking the PAR-2 receptor, adhesion to injured vessels is reduced with a consequent reduction in neointima formation.
Tennant
Gail M
GM
Division of Physiology and Pharmacology, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK.
Wadsworth
Roger M
RM
Kennedy
Simon
S
D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology / Q000293:injuries / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000276:immunology* / Q000378:metabolism*; D017536:Carotid Artery, Common / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D005260:Female; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044464:Receptor, PAR-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism*; D014661:Vasoconstriction / Q000276:immunology; D014664:Vasodilation / Q000276:immunology
D044464:Receptor, PAR-2