In vitro cholesterol synthesis in freshly isolated mononuclear cells of human blood: effect of in vivo administration of clofibrate and/or cholestyramine.
The rate of incorporation of [2-14C]acetate into cholesterol has been measured in freshly isolated peripheral blood mononuclear leukocytes from patients on various hypolipidemic drugs that affect whole body cholesterol synthesis. These studies have demonstrated a significant two-fold increase in mononuclear cell cholesterol synthesis rates in patients receiving cholestyramine, a response measurable after 10 days of drug treatment. Mononuclear cell cholesterol synthesis rates were also measured in four groups of patients on the following drug regimens: 1) no medication, 2) clofibrate (2 g/day), 3) cholestyramine (16 g/day) or 4) both clofibrate and cholestyramine. The results demonstrated that the rate of acetate incorporation into cholesterol was significantly greater in the mononuclear cells from patients receiving either cholestyramine (P less than 0.005) or clofibrate plus cholestyramine (P less 0.001), as compared to controls. Patients receiving clofibrate alone did not differ significantly from controls in their rates of mononuclear cell cholesterol synthesis. Factors other than plasma lipoprotein and lipid levels appeared to be responsible for the elevated sterol synthesis rates observed in all patients receiving cholestyramine.