Effects of peroxisome proliferator-activated receptor alpha/delta agonists on HDL-cholesterol in vervet monkeys.
The objective of this study was to demonstrate the efficacy of a novel peroxisome proliferator-activated receptor (PPAR) agonist and known PPARalpha and PPARdelta 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 PPARdelta selective agonist GW501516 (GW); c) the PPARalpha/delta agonist T913659 (T659); and d) the PPARalpha 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 PPARalpha and PPARdelta 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 PPARalpha and PPARdelta agonists (both mixed and selective) have beneficial effects on HDL-C in these experimental primates.
Wallace
Jeanne M
JM
Department of Pathology/Comparative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. jmwallac@wfubmc.edu
Schwarz
Margrit
M
Coward
Peter
P
Houze
Jonathan
J
Sawyer
Janet K
JK
Kelley
Kathryn L
KL
Chai
Anne
A
Rudel
Lawrence L
LL
D000818:Animals; D002522:Chlorocebus aethiops; D008076:Cholesterol, HDL / Q000097:blood*; D008297:Male; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010316:Particle Size; D013844:Thiazoles / Q000494:pharmacology
D008076:Cholesterol, HDL; C425931:GW 501516; D047493:PPAR alpha; D047495:PPAR gamma; D013844:Thiazoles