Single injection of P-selectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice

Background - Emerging data suggest that P-selectin, by controlling adhesion of white blood cells, may be important in limiting the response to vascular injury. Methods and Results - We tested the hypothesis that transient inhibition of P-selectin with either anti - P-selectin monoclonal antibody (mAb) or anti - P-selectin glycoprotein ligand-1 ( PSGL-1) mAb would reduce neointima formation in the setting of carotid denudation injury in atherosclerosis-prone apolipoprotein E-/- mice. Neointima formation at 28 days was reduced significantly, by 50% or 80%, by a single injection on the day of injury of 100 or 200 mug P-selectin mAb RB 40.34 and by 55% by a single injection of 100 mug PSGL-1 mAb 4RA10 ( P less than or equal to 0.005). In addition, there was a significant reduction in neointimal macrophage content. Conclusions - These findings demonstrate that transient P-selectin or PSGL-1 blockade at the time of arterial injury significantly limits plaque macrophage content and neointima formation in a dose-dependent manner after carotid denudation injury in apolipoprotein E-/- mice.