INVESTIGADORES
SCHUMAN Mariano Luis
congresos y reuniones científicas
Título:
Participation of Cardiac Thyrotropin-Releasing Hormone (cTRH) in myocardial regeneration in rodents
Autor/es:
SCHUMAN, MARIANO LUIS; AISICOVICH, MAIA; LANDRO, MICAELA; ROSATI MACARENA; RODRIGUEZ, MARIA FERNANDA; LANDA, MARÍA SILVINA; GARCÍA, SILVIA INÉS
Lugar:
La plata
Reunión:
Congreso; ISHR Annual Meeting; 2022
Institución organizadora:
International Society of Heart Research
Resumen:
We have recently demonstratedthat cTRH inhibition after myocardial infarction attenuates ischemic damage andventricular remodeling, and improves cardiac function in rats. These, plusprevious results, suggest that cTRH is a relevant mediator in cardiacpathophysiology. It is known that the heart of adult mammals has almost no abilityto regenerate after injury. On the contrary, it has been reported that theheart of neonatal rodents has the ability to completely regenerate aftermyocardial infarction or resection, which is lost after postnatal day 7. Still,the molecular mechanisms that allow this regeneration remain unknown.Objectives: We hypothesized that cTRH is required for cardiac regeneration, andits inhibition would attenuate or prevent cardiac regeneration in rat neonates.We performed apical resection of the heart on postnatal day 1, and a specificsiRNA against TRH was injected in the ventricle to inhibit cTRH expression. ScrambledsiRNA was used for controls. Animals were sacrificed at days 1, 4, 7, 14 and 21post-surgery (PS), and cTRH was analyzed during the time that the heartregenerates. We measured cTRH and cardiac regeneration marker genes expression byRT-PCR in heart tissue. We observed that the cTRH system is over-expressed onlyin the tissue that is in the process of regeneration after resection of theapex of the heart (Days 1, 4 and 7 PS). The specific inhibition of cTRHprevented the increase in the expression of regeneration markers beta catenin,MEIS1 and Cyclin D1.Interestingly, in thisregeneration model, cTRH expression was significantly augmented only in theframe time in which the tissue has regenerative ability. Its specific inhibitionprevented the increase of regeneration markers expression, demonstrating itsparticipation in the process. These results reveal cTRH as a novel target involved in thegeneral regeneration pathway thatshould be considered in the challenge of achieving total regeneration of cardiac tissue in the adult.