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

Background—Pharmacological blockade of 3-integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, 3-integrin–deficient ( 3 / ) mice are not protected from neointimal lesion formation after arterial injury. We investigated this discrepancy in 3 / and wild-type ( 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 3 / and 3 / mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in 3 / mice compared with 3 / mice at intervals up to 3 months. Lesion reduction in 3 / mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with 3 / mice, consistent with reduced SMC migration from the media into the intima of 3 / mice. Moreover, combined eccentric medial disruption and ligation of the carotid in 3 / mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from 3 / mice into irradiated 3 / mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of v 3 and not IIb 3 in the attenuated response. Conclusions—The v 3-integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation. (Circulation. 2004;109:1564-1569.)