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Action of Ciprofibrate in Type IIB Hyperlipoproteinemia: Modulation of the Atherogenic Lipoprotein Phenotype and Stimulation of High-Density Lipoprotein-Mediated Cellular Cholesterol Efflux

Institut National de la Santé et de la Recherche Médicale Unité 551, Dyslipoproteinemia and Atherosclerosis (M.G., W.L.G., E.F., S.S., D.M., M.J.C.), and Service d’Endocrinologie-Métabolisme (E.B.), Hôpital de la Pitié, 75651 Paris, France

Address all correspondence and requests for reprints to: Dr. Maryse Guerin, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 551, Hôpital de la Pitié, Pavillon Benjamin Delessert, 83, Boulevard de l’Hôpital, 75651 Paris Cedex 13, France. E-mail: mguerin{at}infobiogen.fr.

The effects of ciprofibrate (100 mg/d) on apolipoprotein (apo)B- and apoAI-containing lipoprotein subclasses, cholesteryl ester (CE) transfer protein activity, and plasma high-density lipoprotein (HDL)-mediated cellular cholesterol efflux were evaluated in 10 patients displaying type IIB hyperlipidemia. Plasma concentrations of large very low-density lipoprotein (VLDL)-1 (Sf 60–400) and of small VLDL-2 (Sf 20–60) were markedly diminished after fibrate treatment (-40%, P = 0.001; and -25%, P = 0.003, respectively). We observed a reduction (-17%; P = 0.005) in plasma low-density lipoprotein (LDL) levels resulting from significant reductions in concentrations of dense LDL particles (-46%; P < 0.0001). Ciprofibrate induced elevation in plasma total HDL (+13%; P = 0.005) levels; such elevation occurred preferentially in HDL-3 (+22%; P = 0.009). Marked reduction in numbers of atherogenic apoB100-containing particle acceptors was associated with a 25% decrease (P < 0.02) in CE transfer protein-mediated CE transfer from HDL. Finally, a significant fibrate-mediated elevation (+13%; P = 0.01 compared with baseline) in the capacity of plasma from type IIB subjects to mediate free cholesterol efflux from scavenger receptor class B, type I-expressing Fu5AH hepatoma cells was observed. In conclusion, the action of ciprofibrate in type IIB dyslipidemia leads to preferential reduction in particle numbers of atherogenic VLDL-1, VLDL-2, and dense LDL and, concomitantly, to elevation in HDL-3 levels that are associated with stimulation of HDL-mediated cellular free cholesterol efflux through the scavenger receptor class B, type I receptor pathway.

This work was supported by INSERM, Sanofi-Synthelabo, and a Research Fellowship (to W.L.G.) from the French Ministry of Research and Technology.

Abbreviations: ABCA1, ATP-binding cassette transporter-1; apo, apolipoprotein; CE, cholesteryl ester; CETP, CE transfer protein; FBS, fetal bovine serum; HDL, high-density lipoprotein(s); HL, hepatic lipase; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein(s); LPL, lipoprotein lipase; PPAR, peroxisome proliferator-activated receptor; SR-BI, scavenger receptor class B, type I; VLDL, very low-density lipoprotein(s).

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