β 3 -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

Abstract

Background— Pharmacological blockade of β 3 -integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, β 3 -integrin–deficient (β 3 −/− ) mice are not protected from neointimal lesion formation after arterial injury. We investigated this discrepancy in β 3 −/− and wild-type (β 3 +/+ ) mice using different models of injury. Methods and Results— After disruption of the carotid with a transluminal probe, there was no significant difference in neointimal thickening between β 3 −/− and β 3 +/+ mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in β 3 −/− mice compared with β 3 +/+ mice at intervals up to 3 months. Lesion reduction in β 3 −/− mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with β 3 +/+ mice, consistent with reduced SMC migration from the media into the intima of β 3 −/− mice. Moreover, combined eccentric medial disruption and ligation of the carotid in β 3 −/− mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from β 3 +/+ mice into irradiated β 3 −/− mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of α v β 3 and not α IIb β 3 in the attenuated response. Conclusions— The α v β 3 -integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation.