Local application of rapamycin inhibits neointimal hyperplasia in experimental vein grafts

Objective To investigate whether rapamycin can reduce neointima formation in a rabbit model of vein grafts.Methods Each of 15 rabbits received a test and a control graft.On the test graft, 0.3 mg of rapamycin in pluronic gel was applied locally.The control graft received pluronic gel only. Grafts were harvested 4 weeks later and underwent morphometric analysis, immunohistochemical analysis as well as flow cytometry analysis. Results In control group,intimal thickness was significantly less than that in test group (63.7±14.0 vs. 77.8±14.9 μm)(P0.05). The progression indices of control group and test group were 29.3±7.2 and 20.1±9.5, respectively(P0.05). The reduction of intimal thickness was associated with the expression of p27kip1 positive cells in the rapamycin treated grafts(P0.05). Conclusion Perivascular application of rapamycin inhibits neointimal hyperplasia of vein grafts in rabbits,which results from increasing of p27kip1 expression.