Journal of Lipid Research, Vol 21, 65-71, Copyright © 1980 by Lipid Research, Inc.
In vitro cholesterol synthesis in freshly isolated mononuclear cells of human blood: effect of in vivo administration of clofibrate and/or cholestyramine
DJ McNamara, NO Davidson and S Fernandez
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.
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