Dietary phytosterols reduce cyclosporine-induced hypercholesterolemia in apolipoprotein E-knockout mice

Cyclosporine-induced hypercholesterolemia is a major concern after solid organ transplantation. Reducing this side effect of cyclosporine by dietary agents may be safe, cost-effective, and attractive to both patients and health professionals. In this study, the interactions between dietary phytosterols (2% w/w) and cyclosporine (0.02% w/w) in regard to blood cyclosporine concentrations, lipoprotein profile, and histological and morphometrical features of atherosclerotic lesions were studied over 14 weeks in apolipoprotein E-knockout mice. Cyclosporine alone increased plasma non-HDL cholesterol, and triglyceride concentrations and reduced HDL-cholesterol levels as compared to controls. However, these changes were not associated with further increases in atherogenesis as compared to controls. Unlike cyclosporine, phytosterols reduced non-HDL cholesterol and atherosclerosis, and increased HDL-cholesterol concentrations, as compared to the control group. The addition of dietary phytosterols to cyclosporine reduced the extent of cyclosporine-induced hypercholesterolemia, but not cyclosporine-induced hypertriglyceridemia. The extent of atherosclerosis in the combination therapy group was significantly lower than that in the control group or cyclosporine-treated group. Blood cyclosporine concentrations were comparable between the two groups of cyclosporine-treated and the combination therapy groups at the end of the study. This study suggests that simultaneous consumption of dietary phytosterols and cyclosporine may attenuate posttransplant hypercholesterolemia associated with the immunosuppressive cyclosporine. Additional studies are required to understand the mechanisms by which dietary phytosterols reduce cyclosporine-induced hypercholesterolemia.