β₃-Integrin Mediates Smooth Muscle Cell Accumulation in Neointima after Carotid Ligation in Mice

Background-Pharmacological blockade of β₃-integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, β₃-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 (β₃^+/+) 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 β₃^-/- and β ₃^+/+ mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in β ₃^-/- mice compared with β₃^+/+ mice at intervals up to 3 months. Lesion reduction in β₃ ^-/- mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with β₃^+/+ mice, consistent with reduced SMC migration from the media into the intima of β₃^-/- mice. Moreover, combined eccentric medial disruption and ligation of the carotid in β₃^-/- mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from β₃^+/+ mice into irradiated β ₃^-/- mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of α _vβ₃ and not α_IIbβ₃ in the attenuated response. Conclusions-The α_vβ ₃-integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation.