Vascular effects of cyclosporine A in vivo and in vitro

The authors have evaluated the in vivo effects of cyclosporine A on the de-endothelialized rabbit carotid artery. Vascular endothelium was gently removed from the common carotid artery of 10 New Zealand White rabbits that then were treated with therapeutic doses of cyclosporine A (15 mg/kg/day), or its vehicle (Cremophor-EL). Significant intimal proliferation was observed in all cases 2 weeks after de-endothelialization. Concomitant cyclosporine A therapy had no significant effect on intimal smooth muscle proliferation, but was associated with 1) intimal smooth muscle vacuolation, 2) an increase in total intimal thickening, because of the presence of numerous macrophage-derived foam cells, and 3) incorporation of 3H-thymidine by neo-intimal monocyte/macrophages. Mean plasma cholesterol levels were moderately increased in both groups. Although this may have contributed to foam cell formation in the cyclosporine-A-treated animals, it was not the sole determinant, as foam-cell-rich lesions were not observed in control animals. In vitro, cyclosporine A reduced the rate of proliferation of rabbit aortic smooth muscle and endothelial cells in a dose-dependent fashion, and induced smooth muscle cell vacuolation. These data suggest that cyclosporine A may contribute to the formation of graft-related atherosclerosis.