B3-Integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice

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