J. Lipid Res.
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A more recent version of this article appeared on May 1, 2005

Papers In Press, published online ahead of print February 16, 2005
J. Lipid Res., doi:10.1194/jlr.M500002-JLR200
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Submitted on January 3, 2005
Revised on February 8, 2005
Accepted on February 9, 2005

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

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

Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157

Corresponding Author: jmwallac{at}wfubmc.edu

The objective of this study was to demonstrate efficacy of a novel PPAR agonist and known PPAR alpha and PPAR delta agonists to raise 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) PPAR delta selective agonist GW501516 (GW), c) PPAR alpha /delta agonist T913659 (T659), and d) PPAR alpha agonist TriCor® (Fenofibrate). No statistically significant changes were seen in body weight, total plasma cholesterol, plasma triglycerides, VLDL-cholesterol, LDL-cholesterol, or apolipoprotein (apo) B concentrations. Each of the PPAR alpha and delta agonists investigated in this study raised plasma HDL-C, apo A-I, and apo A-II concentrations and increased HDL particle size in St Kitts vervets. The maximum percent 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, while Fenofibrate showed increases in large sized HDL particles. These data provide additional evidence that PPAR alpha and delta agonists (both mixed and selective) have beneficial effects on HDL-C in these experimental primates.


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