β₃-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 β₃-integrins, α_vβ₃ and α_IIbβ₃ (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. Methods and Results - The responses in wild-type mice, β₃-integrin-deficient mice, and P-selectin-deficient mice were studied in a model of transluminal endothelial injury of the femoral artery. At 4 weeks, β₃-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 β₃-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 β₃-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.