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 re- ceptor (PPAR) agonist and known PPARand PPARago- nists 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 PPARselective agonist GW501516 (GW); c ) the PPAR � / � agonist T913659 (T659); and d ) the PPARagonist 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 PPARand PPARagonists investigated in this study increased plasma HDL-C, apoA-I, and apoA-II concen- trations 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 re- sulted in an increase in medium-sized HDL particles, whereas fenofibrate showed increases in large HDL particles. These data provide additional evidence that PPARand PPAR � agonists (both mixed and selective) have beneficial effects on HDL-C in these experimental primates. —Wallace, J. M., M. Schwarz, P. Coward, J. Houze, J. K. Sawyer, K. L. Kelley, A. Chai, and L. L. Rudel. Effects of peroxisome prolifera- tor-activated receptor � / � agonists on HDL-cholesterol in vervet monkeys. J. Lipid Res. 2005. 46: 1009-1016.