CONICET | Buscador de Institutos y Recursos Humanos

We have recently demonstrated that cTRH inhibition after myocardial infarction attenuates ischemic damage and ventricular remodeling, and improves cardiac function in rats. These, plus previous results, suggest that cTRH is a relevant mediator in cardiac pathophysiology. It is known that the heart of adult mammals has almost no ability to regenerate after injury. On the contrary, ithas beenreported that the heart of neonatal rodents has the ability to completely regenerate after myocardial 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 regenerationin rat neonates. We performedapical resection of the heart on postnatal day 1, and a specific siRNA against TRH was injected in the ventricle to inhibit cTRH expression. Scrambled siRNA 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 heart regenerates.We measured cTRH and cardiac regeneration marker genes expression by RT-PCR in heart tissue. We observed that the cTRH system is over-expressed only in the tissue that is in the process of regeneration after resection of the apex of the heart (Days 1,4 and 7 PS). The specific inhibition of cTRH prevented the increase in the expression of regeneration markers beta catenin, MEIS1 and Cyclin D1.Interestingly, in this regeneration model, cTRH expression was significantly augmented only in the frame time in which the tissue hasregenerative ability. Its specific inhibition prevented the increase of regeneration markers expression, demonstrating its participation in the process. These results reveal cTRH as a novel target involved in the general regeneration pathway that should be considered in the challenge of achieving total regeneration of cardiac tissue in the adult.