title: The effect of fenofibrate treatment on endothelium-dependent relaxation induced by oxidative modified low density lipoprotein from hyperlipidemic patients.
abstract: The objective of the research project was to investigate whether fenofibrate treatment may alter the biochemical content of the oxidized LDL and consequently its ability to impair the endothelium-dependent relaxation in hyperlipidemic patients. We hypothesized that fenofibrate treatment of hyperlipidemic patients may attenuate the ability of their oxidized LDL to impair the endothelium-dependent relaxation of the blood vessels as a consequence of fenofibrate-induced changes to the content and composition of lysoPC in the LDL molecule. Hyperlipidemic patients (Type IIb and Type IV) were recruited from the Lipid Clinic, HSC, Winnipeg, Canada, for this study. A blood sample was taken immediately after the recruitment, a second sample was taken after 6 weeks of dietary treatment, and a third sample was taken after 8 weeks of fenofibrate treatment. LDL was isolated from the plasma and oxidized by copper sulfate. Fenofibrate was shown to be highly effect in the reduction of total cholesterol, LDL cholesterol and triglycerides in these patients. Fenofibrate treatment also caused the attenuation of impairment of endothelium-dependent relaxation by the oxidized LDL from these patients. A slight reduction of lysophosphatidylcholine level was also found in the oxidized LDL of the fenofibrate treated patients, relative to LDL isolated after dietary treatment. In addition there were no changes in the fatty acid levels of the lysophosphatidylcholine isolated from LDL. Taken together, our results suggest that while the reduced lysophosphatidylcholine levels may contribute to the attenuated impairment of the endothelium-dependent relaxation of the aortic ring, other unidentified factors impacted by fenofibrate are likely to contribute to the attenuated effects.
authors.affiliation: The Lipid, Lipoprotein and Atherosclerosis Research Group, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Liang
authors.forename: J C
authors.initials: JC
authors.lastname: McMaster
authors.forename: E A
authors.initials: EA
authors.lastname: Kroeger
authors.forename: G M
authors.initials: GM
authors.lastname: Hatch
authors.forename: D
authors.initials: D
authors.lastname: Mymin
authors.forename: T
authors.initials: T
authors.lastname: Dembinski
authors.forename: G
authors.initials: G
authors.lastname: Arthur
authors.forename: G
authors.initials: G
authors.lastname: Shen
authors.forename: R Y
authors.initials: RY
authors.lastname: Man
authors.forename: P C
authors.initials: PC
authors.lastname: Choy
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002849:Chromatography, Gas / Q000379:methods; D004730:Endothelium, Vascular / Q000502:physiology*; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000502:physiology*
chemical_list: D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D008055:Lipids; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D014280:Triglycerides; D002784:Cholesterol; D000109:Acetylcholine; D011345:Fenofibrate