Participation of Cardiac Thyrotropin-Releasing Hormone (cTRH) in myocardial regeneration in rodents

SCHUMAN, ML; AISICOVICH, M.; LANDRO, M. ; ROSATI, M; FERNANDEZ, F.; LANDA, M.S.; GARCIA, SI

La PLata

Congreso; ISHR Annual Meeting 2022; 2022

We have recently demonstrated that cTRH inhibitionafter myocardial infarction attenuates ischemic damage and ventricularremodeling, and improves cardiac function in rats. These, plus previousresults, suggest that cTRH is a relevant mediator in cardiac pathophysiology.It is known that the heart of adult mammals has almost no ability to regenerateafter injury. On the contrary, it has been reported that the heart of neonatalrodents has the ability to completely regenerate after myocardial infarction orresection, which is lost after postnatal day 7. Still, the molecular mechanismsthat allow this regeneration remain unknown. Objectives: We hypothesized that cTRHis required for cardiac regeneration, and its inhibition would attenuate orprevent cardiac regeneration in rat neonates. We performed apical resection ofthe heart on postnatal day 1, and a specific siRNA against TRH was injected inthe ventricle to inhibit cTRH expression. Scrambled siRNA was used for controls.Animals were sacrificed at days 1, 4, 7, 14 and 21 post-surgery (PS), and cTRHwas analyzed during the time that the heart regenerates. We measured cTRH and cardiac regeneration markergenes expression by RT-PCR in heart tissue. We observed that the cTRH system isover-expressed only in the tissue that is in the process of regeneration afterresection of the apex of the heart (Days 1, 4 and 7 PS). The specific inhibitionof cTRH prevented the increase in the expression of regeneration markers betacatenin, MEIS1 and Cyclin D1.Interestingly, in this regeneration model, cTRH expressionwas significantly augmented only in the frame time in which the tissue has regenerativeability. Its specific inhibition prevented the increase of regeneration markersexpression, demonstrating its participation in the process. These results revealcTRH as a novel target involved in the general regeneration pathwaythat should be consideredin the challenge of achieving totalregeneration of cardiac tissue in the adult.