on October 13, 2005
Published online before print October 13, 2005, doi: 10.1161/01.ATV.0000190700.76493.bb
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Submitted on November 23, 2004
Accepted on October 3, 2005
Effect of Fenofibrate on Plasma Lipoprotein Composition and Kinetics in Patients With Complete Hepatic Lipase Deficiency
Isabelle L. Ruel ;
From the Institute on Nutraceuticals and Functional Foods (I.L.R., B.L., J.-F.M.), Laval University, Québec, Canada; the Lipid Research Center (I.L.R., B.L., J.-F.M., P.C.), CHUL Research Center, Québec, Canada; the Department of Medicine and Center for Experimental Therapeutics (K.O.B.), University of Pennsylvania School of Medicine, Philadelphia, Pa; the Hyperlipidemia and Atherosclerosis Research Group (J.S.C.), Clinical Research Institute of Montréal, Canada; and the Cardiovascular Genetics Laboratory (M.M.), Royal Victoria Hospital, McGill University Health Center, Montréal, Canada.
* To whom correspondence should be addressed. E-mail: patrick.couture{at}crchul.ulaval.ca.
Objective--The goal of this study was to characterize the effect of microcoated fenofibrate (160 mg/day for 6 months) on plasma lipoprotein composition and kinetics in 2 patients with complete hepatic lipase (HL) deficiency.
Methods and Results--Fenofibrate treatment normalized the plasma lipoprotein profile of patients with complete HL deficiency, as evidenced by significant reductions in the plasma concentration of cholesterol (-49%) and triglycerides (-82%) and a significant increase in low-density lipoprotein (LDL) size (251.5±1.8 versus 263.5±0.7 Å). The in vivo kinetics of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL apolipoprotein (apo)B-100 and plasma apoA-I and apoA-II were studied using a primed-constant infusion of L-[5,5,5-D3]-leucine for 12 hours in the fasted state. Fenofibrate treatment in complete HL-deficient patients substantially decreased plasma concentrations of VLDL, IDL, and LDL apoB-100 attributable to important increases in VLDL (+325%), IDL (+129%), and LDL (+218%) apoB-100 fractional catabolic rates (FCR). IDL apoB-100 FCR nevertheless remained 60% lower after treatment compared with values obtained in controls (n=5). The kinetics of plasma apoA-I and apoA-II as well as the capacity of total plasma and of high-density lipoprotein particles to efflux cellular cholesterol from normal human skin fibroblasts was not altered by fenofibrate.
Conclusion--Fenofibrate therapy exerts a pronounced antiatherogenic effect on triglyceride-rich lipoproteins even in the complete absence of HL.
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