Beta(3)-integrin-deficient mice but not P-selectin-deficient mice develop intimal hyperplasia after vascular injury: correlation with leukocyte recruitment to adherent platelets 1 hour after injury.
BACKGROUND
Intimal hyperplasia contributes to restenosis after percutaneous vascular interventions. Both beta(3)-integrins, alpha(V)beta(3) and alpha(IIb)beta(3) (glycoprotein IIb/IIIa), and leukocytes have been implicated in neointimal formation, based in part on the results obtained using antagonists to 1 or both receptors in animal models.


RESULTS
The responses in wild-type mice, beta(3)-integrin-deficient mice, and P-selectin-deficient mice were studied in a model of transluminal endothelial injury of the femoral artery. At 4 weeks, beta(3)-integrin-deficient mice were not protected from developing intimal hyperplasia, whereas P-selectin-deficient mice were protected. Within 1 hour of injury, several layers of platelets deposited on the arteries of wild-type mice and a single layer of platelets deposited on the vessels of beta(3)-integrin-deficient mice; in both cases, leukocytes were recruited to the platelet layer. In P-selectin-deficient mice, the platelet layer was less compact and extended further into the lumen but did not recruit leukocytes.


CONCLUSIONS
In a model of transluminal arterial injury, absence of early leukocyte recruitment and not deficiency of beta(3)-integrins correlated with a reduction in neointimal formation. Blockade of P-selectins may be an effective therapeutic strategy to decrease restenosis after percutaneous vascular interventions.
Smyth
S S
SS
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Reis
E D
ED
Zhang
W
W
Fallon
J T
JT
Gordon
R E
RE
Coller
B S
BS
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology* / Q000648:ultrastructure; D006965:Hyperplasia; D039661:Integrin beta3; D007962:Leukocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008854:Microscopy, Electron; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
D015703:Antigens, CD; D039661:Integrin beta3; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins