Activation of Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma) Through NF-kappa B/Brg1 and TGF-beta(1) Pathways Attenuates Cardiac Remodeling in Pressure-Overloaded Rat Hearts

Background/Aims: Cardiac remodeling is a common pathophysiological change along with chronic hypertension and myocardial infarction. Recent evidence indicated that cardiac tissue expressed peroxisome proliferator-activated receptor gamma (PPAR gamma). However, the functional role of PPAR gamma in cardiac remodeling remained unclear. The present study was designed to investigate the relationship between PPAR gamma activation and pressure overload-induced cardiac remodeling. Methods: Cardiac remodeling model was successfully established by abdominal aorta ligation. Cardiac fibrosis and cardiomyocyte hypertrophy were simulated by 100 nM angiotensin II (Ang II) in vitro. Haemodynamic parameters, the expressions of Brg1, alpha-MHC, beta-MHC, transforming growth factor beta 1 (TGF-beta(1)), collagen-I, collagen-III and NF-kappa B were examined. Results: Morphological and haemodynamic measurements showed that the activation of PPAR gamma improved the impaired cardiac function and decreased interstitial fibrosis in cardiac remodeling rats. Further results also showed that the activation of PPAR gamma inhibited the expressions of Brg1 and TGF-beta(1) in the cardiac remodeling hearts. The activation of PPAR gamma also inhibited the proliferation and collagen production of cardiac fibroblasts, and down-regulated the activity of Brg1 and the expression of TGF-beta(1) induced by Ang II in cultured neonatal rat cardiomyocytes and cardiac fibroblasts, respectively, through NF-kappa B pathway. Conclusions: These results suggested that PPAR gamma activation effectively inhibited cardiac remodeling processes by suppression of Brg1 and TGF-beta(1) expressions through NF-kappa B pathway in the pressure-overloaded hearts induced by abdominal aorta ligation in rats. (C) 2015 S. Karger AG, Basel