Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts

Objective: Rapamycin is an immunosuppressive agent with marked anti proliferative properties and is effective in reducing in stent restenosis and vein graft neointimal. hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the rote of apoptosis in rapamycin treated vein grafts in a mouse model. Methods: C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200 mug of rapamycin were applied locally in pluronic get. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL). Results: In grafted veins without treatment (controls) neointimal thickness was 50 (12-58) mum at 4 weeks postoperatively. In 200 mug rapamycin treated grafts the neointimal thickness was 17 (5-55) mum. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was tower in both groups with no significant difference between rapamycin treated grafts and controls. Conclusion: We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease. (C) 2004 Elsevier B.V. All rights reserved.