Cardioprotective Effects of a PPAR-delta Selective Agonist (GW610742X) in a Rodent Model of Congestive Heart Failure
Hu T, Williams C, Lenhard S, Schaeffer T, Grill A, Doe C, Willette R, Jucker B, Olzinski A, Maniscalco K
Medical College of Georgia, GlaxoSmithKline
PPAR-&[delta] nuclear receptor is a transcriptional regulator for nutrient metabolism and energy homeostasis and cardiac specific knockout of PPAR-&[delta] results in cardiac lipotoxicity, hypertrophy, and failure. In this study, we examined the potential therapeutic benefit of a specific PPAR-&[delta] agonist (GW610742X) on cardiac LV and RV functional parameters, energetics and substrate metabolism in a rodent model of congestive heart failure. GW610742X treatment resulted in a reduction in RV hypertrophy, pulmonary congestion, and a normalization of substrate metabolism in a rodent model of congestive heart failure.