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 alp ha (IIb)beta (3) (glycoprotein IIb/IIIa), and leukocytes have been implicat ed in neointimal formation, based in part on the results obtained using ant agonists to 1 or both receptors in animal models. Methods and Results-The responses in wild-type mice, beta (3)-integrin-defi cient mice, and P-selectin-deficient mice were studied in a model of transl uminal endothelial injury of the femoral artery, At 4 weeks, beta (3)-integ rin-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 la yer. 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 le ukocyte recruitment and not deficiency of beta (3)-integrins correlated wit h a reduction in neointimal formation. Blockade of P-selectins may be an ef fective therapeutic strategy to decrease restenosis after percutaneous vasc ular interventions.