Pitavastatin Inhibits Intimal Hyperplasia in Rabbit Vein Graft

Abstract

The autologous saphenous vein graft is currently the most suitable conduit for arterial bypass of the lower limbs. Various approaches have been attempted to control vein graft intimal hyperplasia, and several recent reports have suggested that statin use may be linked to improved patency of vein grafts. In this study, the efficacy of pitavastatin was evaluated on intimal hyperplasia and midkine expression of experimental normocholesterolemic rabbit autologous vein graft. Rabbits were fed regular rabbit chow, and in half of them, pitavastatin (1 mg/kg/d) was administered. A week after starting the treatment, jugular vein was implanted into the carotid artery. At 2 and 4 wk after the operation, vein grafts were harvested, and intimal hyperplasia of vein grafts were assessed. Cell proliferation in neointima was determined by proliferative cell nuclear antigen and Ki-67 stain 2 wk after implantation. In addition, the effect of pitavastatin on midkine, a heparin-binding growth factor, expressed in vein grafts was analyzed by Western blotting. The intimal hyperplasia in the pitavastatin group was significantly suppressed compared with the control group. Both proliferative cell nuclear antigen and Ki-67 labeling index were significantly lower in the pitavastatin group, and pitavastatin significantly reduced midkine expression of vein graft. These results demonstrate the efficacy of pitavastatin in reducing the degree of intimal hyperplasia of rabbit autologous vein grafts under normocholesterolemic condition. The mechanism of inhibition of intimal hyperplasia might be associated with midkine suppression.