出版社:American Society for Biochemistry and Molecular Biology
摘要:The objective of this study was to demonstrate the efficacyof a novel peroxisome proliferator-activated receptor (PPAR)agonist and known PPAR and PPAR agonists to increase HDL-cholesterol(HDL-C) in the St. Kitts vervet, a nonhuman primate model ofatherosclerosis. Four groups (n = 6) were studied and each groupwas assigned one of the following "treatments": a) vehicle only(vehicle); b) the PPAR selective agonist GW501516 (GW); c) thePPAR/ agonist T913659 (T659); and d) the PPAR agonist TriCor®(fenofibrate). No statistically significant changes were seenin body weight, total plasma cholesterol, plasma triglycerides,VLDL-C, LDL-C, or apolipoprotein B (apoB) concentrations. Eachof the PPAR and PPAR agonists investigated in this study increasedplasma HDL-C, apoA-I, and apoA-II concentrations and increasedHDL particle size in St. Kitts vervets. The maximum percentageincrease in HDL-C from baseline for each group was as follows:vehicle, 5%; GW, 43%; T659, 43%; and fenofibrate, 20%. Treatmentwith GW and T659 resulted in an increase in medium-sized HDLparticles, whereas fenofibrate showed increases in large HDLparticles.
These data provide additional evidence that PPAR and PPAR agonists(both mixed and selective) have beneficial effects on HDL-Cin these experimental primates.Supplementary key words animal model • apolipoprotein A-I • apolipoprotein A-II • atherosclerosis • high density lipoprotein particle size • lipoprotein metabolism • nonhuman primate