| First Author | Palioura D | Year | 2023 |
| Journal | J Mol Cell Cardiol | Volume | 183 |
| Pages | 27-41 | PubMed ID | 37603971 |
| Mgi Jnum | J:341160 | Mgi Id | MGI:7532444 |
| Doi | 10.1016/j.yjmcc.2023.08.005 | Citation | Palioura D, et al. (2023) PPARdelta activation improves cardiac mitochondrial homeostasis in desmin deficient mice but does not alleviate systolic dysfunction. J Mol Cell Cardiol 183:27-41 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR) delta is a major transcriptional regulator of cardiac energy metabolism with pleiotropic properties, including anti-inflammatory, anti-oxidative and cardioprotective action. In this study, we sought to investigate whether pharmacological activation of PPARdelta via intraperitoneal administration of the selective ligand GW0742 could ameliorate heart failure and mitochondrial dysfunction that have been previously reported in a characterized genetic model of heart failure, the desmin null mice (Des(-/-)). Our studies demonstrate that treatment of Des(-/-) mice with the PPARdelta agonist attenuated cardiac inflammation, fibrosis and cardiac remodeling. In addition, PPARdelta activation alleviated oxidative stress in the failing myocardium as evidenced by decreased ROS levels. Importantly, PPARdelta activation stimulated mitochondrial biogenesis, prevented mitochondrial and sarcoplasmic reticulum vacuolar degeneration and improved the mitochondrial intracellular distribution. Finally, PPARdelta activation alleviated the mitochondrial respiratory dysfunction, prevented energy depletion and alleviated excessive autophagy and mitophagy in Des(-/-) hearts. Nevertheless, improvement of all these parameters did not suffice to overcome the significant structural deficiencies that desmin deletion incurs in cardiomyocytes and cardiac function did not improve significantly. In conclusion, pharmacological PPARdelta activation in Des(-/-) hearts exerts protective effects during myocardial degeneration and heart failure by preserving the function and quality of the mitochondrial network. These findings implicate PPARdelta agonists as a supplemental constituent of heart failure medications. |
