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  • 标题:Effects of peroxisome proliferator-activated receptor {alpha}/{delta} agonists on HDL-cholesterol in vervet monkeys
  • 本地全文:下载
  • 作者:Wallace, Jeanne M. ; Schwarz, Margrit ; Coward, Peter
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2005
  • 卷号:46
  • 期号:05
  • 页码:1009-1016
  • DOI:10.1194/jlr.M500002-JLR200
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:The objective of this study was to demonstrate the efficacy of a novel peroxisome proliferator-activated receptor (PPAR) agonist and known PPAR{alpha} and PPAR{delta} agonists to increase HDL-cholesterol (HDL-C) in the St. Kitts vervet, a nonhuman primate model of atherosclerosis. Four groups (n = 6) were studied and each group was assigned one of the following "treatments": a) vehicle only (vehicle); b) the PPAR{delta} selective agonist GW501516 (GW); c) the PPAR{alpha}/{delta} agonist T913659 (T659); and d) the PPAR{alpha} agonist TriCor® (fenofibrate). No statistically significant changes were seen in body weight, total plasma cholesterol, plasma triglycerides, VLDL-C, LDL-C, or apolipoprotein B (apoB) concentrations. Each of the PPAR{alpha} and PPAR{delta} agonists investigated in this study increased plasma HDL-C, apoA-I, and apoA-II concentrations and increased HDL particle size in St. Kitts vervets. The maximum percentage increase in HDL-C from baseline for each group was as follows: vehicle, 5%; GW, 43%; T659, 43%; and fenofibrate, 20%. Treatment with GW and T659 resulted in an increase in medium-sized HDL particles, whereas fenofibrate showed increases in large HDL particles. These data provide additional evidence that PPAR{alpha} and PPAR{delta} agonists (both mixed and selective) have beneficial effects on HDL-C in these experimental primates. Supplementary key words animal model • apolipoprotein A-I • apolipoprotein A-II • atherosclerosis • high density lipoprotein particle size • lipoprotein metabolism • nonhuman primate
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