β 3 -Integrin–Deficient Mice but Not P-Selectin–Deficient Mice Develop Intimal Hyperplasia After Vascular Injury

Abstract

Background —Intimal hyperplasia contributes to restenosis after percutaneous vascular interventions. Both β 3 -integrins, α V β 3 and α IIb β 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. Methods and Results —The responses in wild-type mice, β 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, β 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 β 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 β 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.