Proteomics Reveals Long-Term Alterations in Signaling and Metabolic Pathways Following Both Myocardial Infarction and Chemically Induced Denervation.

Autor: Salem JB; INSERM DR Midi-Pyrénées Limousin, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) UMR1297, Université de Toulouse III, Toulouse, France.; Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, QC, J2S 2M2, Canada.; Centre de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montréal, QC, Canada., Iacovoni JS; INSERM DR Midi-Pyrénées Limousin, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) UMR1297, Université de Toulouse III, Toulouse, France., Calise D; INSERM DR Midi-Pyrénées Limousin, Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales Service Microchirurgie, (CREFRE- US06, Rangueil), Toulouse, France., Arvanitis DN; INSERM DR Midi-Pyrénées Limousin, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) UMR1297, Université de Toulouse III, Toulouse, France. constandina.arvanitis@univ-tlse3.fr.; Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) UMR INSERM 1297 - Équipe 10, 1 Avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex, France. constandina.arvanitis@univ-tlse3.fr., Beaudry F; Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, QC, J2S 2M2, Canada. francis.beaudry@umontreal.ca.; Centre de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montréal, QC, Canada. francis.beaudry@umontreal.ca.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2022 Aug; Vol. 47 (8), pp. 2416-2430. Date of Electronic Publication: 2022 Jun 18.
DOI: 10.1007/s11064-022-03636-7
Abstrakt: Myocardial infraction (MI) is the principal risk factor for the onset of heart failure (HF). Investigations regarding the physiopathology of MI progression to HF have revealed the concerted engagement of other tissues, such as the autonomic nervous system and the medulla oblongata (MO), giving rise to systemic effects, important in the regulation of heart function. Cardiac sympathetic afferent denervation following application of resiniferatoxin (RTX) attenuates cardiac remodelling and restores cardiac function following MI. While the physiological responses are well documented in numerous species, the underlying molecular responses during the initiation and progression from MI to HF remains unclear. We obtained multi-tissue time course proteomics with a murine model of HF induced by MI in conjunction with RTX application. We isolated tissue sections from the left ventricle (LV), MO, cervical spinal cord and cervical vagal nerves at four time points over a 12-week study. Bioinformatic analyses consistently revealed a high statistical enrichment for metabolic pathways in all tissues and treatments, implicating a central role of mitochondria in the tissue-cellular response to both MI and RTX. In fact, the additional functional pathways found to be enriched in these tissues, involving the cytoskeleton, vesicles and signal transduction, could be downstream of responses initiated by mitochondria due to changes in neuronal pulse frequency after a shock such as MI or the modification of such frequency communication from the heart to the brain after RTX application. Development of future experiments, based on our proteomic results, should enable the dissection of more precise mechanisms whereby metabolic changes in neuronal and cardiac tissues can effectively ameliorate the negative physiological effects of MI via RTX application.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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