Atherosclerosis, 79 (1989) 253-255 Elsevier Scientific Publishers Ireland, Ltd. ATHERO 253 Preliminary Note Inhibition of cholesterol biosynthesis in freshly isolated blood mononuclear cells from normolipidemic subjects and hypercholesterolemic patients treated with bezafibrate Roberto Cosentini I, Francesco Blasi ‘, Marco Trinchera 2, Domenico Sommariva 3 and Angelo Fasoli ’ ’ Institute of Internal Medicine and Medical Physiopathologv, and 2 Department of Chemistty and Medical Biochemistty, University of Milan, ’ II Department of Medicine, L. Sacco Hospital, Milan (Itaryi (Received 31 January, 1989) (Revised, received 5 June, 1989) (Accepted 5 June, 1989) Summary Bezafibrate was given for 15 days at a dose of 200 mg t.i.d. to 4 normolipidemic subjects, to 5 patients with putative heterozygous familial hypercholesterolemia, and to 6 patients with primary hypercholestero- lemia of the non-familial type. At the end of the treatment, the rate of incorporation of labelled acetate into non-saponifiable lipids in freshly isolated blood mononuclear cells decreased in all subjects. On the average, acetate incorporation decreased by 31% in cells from normolipidemic subjects, 41% in cells from familial, and 45% in cells from non-familial hypercholesterolemia patients. Results of the present study suggest that the lowering effect of bezafibrate on serum cholesterol is mainly due to the inhibition of cholesterol synthesis through the suppression of HMG-CoA reductase as was demonstrated in rat hepatocytes and in cultured human blood mononuclear cells. Key words: Bezafibrate; Serum cholesterol; Cholesterol synthesis; Blood mononuclear cells Introduction Bezafibrate has multiple effects on lipid metabolism. It decreases hepatic synthesis and secretion of very low density lipoproteins (VLDL) [l] and has been found to inhibit cholesterol Correspondence to: Domenico Sommariva, Ospedale L. Sacco. Via G.B. Grassi. 74. 20157 Milano, Italy. synthesis by depressing 3-hydroxy-3-methyl- glutaryl-coenzyme A (HMG-CoA) reductase activ- ity [2,3]. So far. however, demonstration of an inhibition of cholesterol synthesis in humans tak- ing bezafibrate is lacking. This prompted us to investigate cholesterol synthesis in blood mono- nuclear cells isolated from normolipidemic and hypercholesterolemic subjects treated with be- zafibrate. The rate of sterol synthesis in freshly isolated mononuclear cells parallels changes in 0021-9150/89/$03.50 0 1989 Elsevier Scientific Publishers Irelana d, Ltd.