Effect of Cyclosporine on Arterial Balloon Injury Lesions in Cholesterol-Clamped Rabbits

Abstract

Abstract —Restenosis after balloon dilatation of stenosed coronary arteries is a major clinical problem. Because T lymphocytes occur in neointima and because cyclosporine inhibits T-lymphocyte proliferation, we tested the hypothesis that cyclosporine would attenuate neointimal proliferation after balloon dilation injury. Rabbits with a balloon-injured aorta, randomized to cyclosporine in the human therapeutic range (n=13) or vehicle (n=14) were followed up for 5 weeks; as a control for the effect of cyclosporine, half the rabbits received in addition an aorta allograft. Rabbits were clamped at a human plasma cholesterol level of 5 to 7 mmol/L. Cyclosporine did not affect aorta cholesterol accumulation or neointimal proliferation in balloon-injured aortas; however, it attenuated both in transplanted aortas. Likewise, cyclosporine had no effect on endothelial cells at balloon-injured sites, but protected these cells in the transplanted aortas. Infiltration of smooth muscle cells, T lymphocytes, and macrophages were unaffected by cyclosporine in balloon-injured aortas; however, in transplanted aortas, cyclosporine reduced the relative number of T lymphocytes and macrophages but increased the relative number of smooth muscle cells. Finally, in balloon-injured aortas, 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 in transplanted aortas. These results suggest that cyclosporine does not attenuate neointimal proliferation after balloon dilatation, and that T lymphocyte—mediated immune responses are not involved in neointimal proliferation after balloon dilatation.