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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2434.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Normal Oxidative Stress and Enhanced Lipoprotein Resistance to In Vitro Oxidation in Hypertriglyceridemia

Effects of Bezafibrate Therapy

Frits H. A. F. de Man; Iris J. A. M. Jonkers; Edzard Schwedhelm; Augustinus H. M. Smelt; Willem Onkenhout; Wim van Duyvenvoorde; Rien Buytenhek; Jan A. Gevers Leuven; Raphael Troost; Arnoud van der Laarse; Hans M. G. Princen

From the Departments of Cardiology (F.H.A.F.d.M., A.v.d.L.), Internal Medicine (I.J.A.M.J., A.H.M.S., J.A.G.L.), and Pediatrics (W.O.), Leiden University Medical Center, and Gaubius Laboratory (W.v.D., R.B., J.A.G.L., H.M.G.P.), TNO Prevention and Health, Leiden, the Netherlands, and the Institute of Clinical Pharmacology (E.S., R.T.), Hannover Medical School, Hannover, Germany.

Correspondence to A. van der Laarse, PhD, Department Cardiology, C5-P, Leiden University Medical Center, PO Box 9600; 2300 RC Leiden, Netherlands. E-mail A.van_der_Laarse{at}lumc.nl

Abstract—Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F₂-isoprostanes (8-isoprostaglandin F₂ and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F₂) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F₂-isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F₂ (762±313 versus 552±245 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.03), whereas 2,3-dinor-5,6-dihydro-8-isoprostaglandin F₂ levels tended to be increased (1714±761 versus 1475±606 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1) HTG is associated with normal in vivo oxidative stress and enhanced ex vivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resistance of lipoproteins to copper-induced oxidation and enhances oxidative stress in HTG patients.

Key Words: hypertriglyceridemia • LDL oxidation • VLDL oxidation • F₂-isoprostanes • bezafibrate

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