The effect of fenofibrate treatment on endothelium-dependent relaxation induced by oxidative modified low density lipoprotein from hyperlipidemic patients

The objective of the research project was to investigate whether fenofibrat e treatment may alter the biochemical content of the oxidized LDL and conse quently its ability to impair the endothelium-dependent relaxation in hyper lipidemic patients. We hypothesized that fenofibrate treatment of hyperlipi demic patients may attenuate the ability of their oxidized LDL to impair th e endothelium-dependent relaxation of the blood vessels as a consequence of fenofibrate-induced changes to the content and composition of lysoPC in th e LDL molecule. Hyperlipidemic patients (Type IIb and Type IV) were recruited from the Lipi d Clinic, HSC, Winnipeg, Canada, for this study. A blood sample was taken i mmediately after the recruitment, a second sample was taken after 6 weeks o f dietary treatment, and a third sample was taken after 8 weeks of fenofibr ate treatment. LDL was isolated from the plasma and oxidized by copper sulf ate. Fenofibrate was shown to be highly effect in the reduction of total ch olesterol, LDL cholesterol and triglycerides in these patients. Fenofibrate treatment also caused the attenuation of impairment of endothelium-depende nt relaxation by the oxidized LDL from these patients. A slight reduction o f lysophosphatidylcholine level was also found in the oxidized LDL of the f enofibrate treated patients, relative to LDL isolated after dietary treatme nt. In addition there were no changes in the fatty acid levels of the lysop hosphatidylcholine isolated from LDL. Taken together, our results suggest t hat 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 con tribute to the attenuated effects.