Effect of cyclosporine on arterial balloon injury lesions in cholesterol-clamped rabbits - T lymphocyte-mediated immune responses not involved in balloon injury-induced neointimal proliferation

Restenosis after balloon dilatation of stenosed coronary arteries is a majo r clinical problem. Because T lymphocytes occur in neointima and because cy closporine inhibits T-lymphocyte proliferation, we tested the hypothesis th at cyclosporine would attenuate neointimal proliferation after balloon dila tion injury. Rabbits with a balloon-injured aorta, randomized to cyclospori ne in the human therapeutic range (n = 13) or vehicle (n = 14) were followe d up for 5 weeks; as a control for the effect of cyclosporine, half the rab bits received in addition an aorta allograft. Rabbits were clamped at a hum an plasma cholesterol level of 5 to 7 mmol/L. Cyclosporine did not affect a orta cholesterol accumulation or neointimal proliferation in balloon-injure d aortas; however, it attenuated both in transplanted aortas. Likewise, cyc losporine had no effect on endothelial cells at balloon-injured sites, but protected these cells in the transplanted aortas. Infiltration of smooth mu scle cells, T lymphocytes, and macrophages were unaffected by cyclosporine in balloon-injured aortas; however, in transplanted aortas, cyclosporine re duced the relative number of T lymphocytes and macrophages but increased th e relative number of smooth muscle cells. Finally, in balloon-injured aorta s, cyclosporine did not affect expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, or major histocompatibility complex II, but all these cellular activation markers were attenuated by cyclosporine i n transplanted aortas. These results suggest that cyclosporine does not att enuate neointimal proliferation after balloon dilatation, and that T lympho cyte-mediated immune responses are not involved in neointimal proliferation after balloon dilatation.