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Journal of Lipid Research, Vol. 46, 1009-1016, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Effects of peroxisome proliferator-activated receptor / agonists on HDL-cholesterol in vervet monkeys

Jeanne M. Wallace^1,*, Margrit Schwarz^2,, Peter Coward, Jonathan Houze, Janet K. Sawyer^*, Kathryn L. Kelley^*, Anne Chai^3, and Lawrence L. Rudel^*

^* Department of Pathology/Comparative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157
Tularik, Inc., South San Francisco, CA 94080

¹ To whom correspondence should be addressed. e-mail: jmwallac{at}wfubmc.edu

The objective of this study was to demonstrate the efficacy of 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 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 selective agonist GW501516 (GW); c) the PPAR/ agonist T913659 (T659); and d) the PPAR 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 and PPAR 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 and PPAR 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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