Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia

• Published in: Atherosclerosis 2012-02, Vol.220 (2), p.470-476
• Main Authors: Choi, Yun-Jung, Roberts, Brian K, Wang, Xueyan, Geaney, J. Casey, Naim, Sue, Wojnoonski, Kathleen, Karpf, David B, Krauss, Ronald M
• Format: Article
• Language: English
• Subjects: Acetates - therapeutic use; agonists; alternative medicine; Analysis of Variance; atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - drug therapy; Atherosclerosis - etiology; Atorvastatin Calcium; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular system; Chi-Square Distribution; Double-Blind Method; Drug Therapy, Combination; Dyslipidemias - blood; Dyslipidemias - complications; Dyslipidemias - drug therapy; Female; HDL; Heptanoic Acids - therapeutic use; high density lipoprotein; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; hyperlipidemia; Hypolipidemic Agents - therapeutic use; LDL; Lipoprotein subfractions; Lipoproteins - blood; low density lipoprotein; Male; Medical sciences; Middle Aged; Obesity - complications; overweight; Overweight - complications; Particle Size; Peroxisome proliferator activated receptor delta; Pharmacology. Drug treatments; phenotype; PPAR gamma - agonists; PPAR gamma - metabolism; Pyrroles - therapeutic use; Small dense LDL; Time Factors; translation (genetics); Treatment Outcome; Triazoles - therapeutic use; Triglyceride; Vasodilator agents. Cerebral vasodilators; very low density lipoprotein; VLDL
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2011.10.029

Abstract Objective Determine the effects of treatment with a selective PPAR-δ agonist ± statin on plasma lipoprotein subfractions in dyslipidemic individuals. Methods Ion mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-δ agonist MBX-8025 (50 and 100 mg/d) ± atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial. Results MBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in ∼90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL–IDL–LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (−24.5 ± 5.3% vs. −47.8 ± 4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL. Conclusion PPAR-δ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia.