Capetanaki Yassemi

Galatou Eleftheria

Lazou Antigone

Mavroidis Manolis

Mellidis Kyriakos

Mouchtouri Eleni-Taxiarchia

Palioura Dimitra

Panteris Emmanuel

English

University of Szeged

 35  8th European Section Meeting of the International Academy of Cardiovascular Sciences (IACS); September 28 – October 1, 2022; Szeged, Hungary PPARβ/δ ACTIVATION PROTECTS FROM MITOCHONDRIAL DEGENERATION, INFLAMMATION AND FIBROSIS IN A GENETIC ANIMAL MODEL OF HEART FAILURE  Dimitra Palioura1, Kyriakos Mellidis1, Eleftheria Galatou1, Eleni-Taxiarchia Mouchtouri2, Emmanuel Panteris3, Manolis Mavroidis2, Yassemi Capetanaki2, Antigone Lazou1  1Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece,  2Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece, 3Department of Botany, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece  PPARβ/δ is a primary transcriptional regulator of cardiac energy metabolism with pleiotropic properties, including anti-inflammatory, anti-oxidative and cardioprotective action. The aim of the present study was to investigate whether pharmacological activation of PPARβ/δ could ameliorate cardiac tissue damage in desmin null mice (Des-/-), a genetic model of heart failure and explore the potential effects on the impaired mitochondrial network. In Des-/- mice, ultrastructural abnormalities with severely damaged mitochondria, massive cardiomyocyte death, an early acute inflammatory response and severe cardiac remodeling lead to dilated cardiomyopathy and eventually heart failure. Our findings demonstrate that PPARβ/δ activation protects from extensive cardiac inflammation, fibrosis and cardiac remodeling, all hallmarks of the Des-/- heart. Importantly, PPARβ/δ activation stimulates mitochondrial biogenesis, protects mitochondria from exacerbated degeneration and improves the deranged mitochondrial network as observed in transmission electron microscopy images of Des-/- hearts. Concomitantly, PPARβ/δ restores the balance in fission/fusion protein markers, attenuates ATP depletion and enhances mitochondrial functionality in Des-/- hearts. Furthermore, PPARβ/δ activation alleviates oxidative stress as evidenced by almost 50% decrease in superoxide levels through transcriptional activation of the antioxidant regulator, Nrf2 and major ROS scavengers, in the failing myocardium. In conclusion, pharmacological activation of PPARβ/δ during myocardial degeneration and heart failure in Des-/- hearts demonstrates cardioprotective action by preserving the structural and functional quality of the mitochondrial network and alleviating inflammation and fibrosis.   Keywords: heart failure; inflammation; mitochondria; peroxisome proliferator-activated receptor β/δ   Funding: This work was supported by the European Union (European Social Fund-ESF) and Greek national funds of the National Strategic Framework (NSRF)- Research funding programme “Cooperation” [09SYN-21-965] and the Operational Program "Human Resources Development, Education and Lifelong Learning" under the call for proposals EDBM 103 “Support for researchers with emphasis on new researchers-cycle B' [MIS 5047852].     

PPARβ/δ activation protects from mitochondrial degeneration, inflammation and fibrosis in a genetic animal model of heart failure : [abstract]

http://acta.bibl.u-szeged.hu/77497/1/iacs_es_2022_035.pdf

PPARβ/δ activation protects from mitochondrial degeneration, inflammation and fibrosis in a genetic animal model of heart failure : [abstract]

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