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Cardiacthyrotropin releasing hormone (TRH) inhibition attenuates the post-ischemic damage and improves ventricular function after myocardial infarct in rats.Mariano L. Schuman, Ludmila Peres Diaz, Jorge Toblli, Maia Aisicovich,Fernando Ingallina, Maria S Landa y Silvia I García.Laboratoryof Molecular Cardiology, Institute of Medical Research A. Lanari, UBA;IDIM-CONICET, Buenos Aires, Argentina. When an injury of the heart occurs (acute myocardial infarction) starts the process ofventricular remodeling, which involves changes in the size, shape and functionof the ventricle, regulated by mechanical, neurohormonal, and genetic factors, consideredthe more important factors for the development of heart failure. Acute myocardialinfarction causes myocyte damage and extracellular matrix activation withinterstitial fibrosis of the infarcted area carrying ventricular dysfunctionand progressive dilatation accompanied by reparative fibrosis in the infarctedzone .A few years ago the presence of thyrotropin-releasing hormone (TRH) in cardiactissue has been demonstrated, but its function is still unknown. Later, we wereable to describe a TRH system hyperactivity in the hypertrophied left ventricle(LV) of spontaneously hypertensive (SHR) adult rat?s hearts. Indeed, TRHinhibition prevents cardiac hypertrophy despite the severe hypertension,suggesting the involvement of the tripeptide in this process (Schuman et al, 2011). Moreover, we observed that overexpression of TRH inthe left ventricle caused by intracardiac injection of a specific plasmid forTRH overexpression (PCMV-TRH) induces features of the hypertrophic phenotype heartin a Normal Wistar rat as hypertrophic markers genes increases (ANP, BNP and β-MHC) (Schumanet al 2014). Furthermore, another laboratory demonstrated a significantincrease in the expression of TRH after the myocardial infarction maneuver,postulating its involvement in this pathology (Jin H. et al 2004). Consequently based on own and others results, we hypothesized that the inhibition of the left ventricle TRH system using siRNA before an infarct, could prevent or attenuate post cardiac remodeling damage.We use Wistar males 20 week-old rats which were subjected to the technique of infarction by permanent ligation of the anterior descending coronary artery after a prior injection of 40ug of SiRNA against TRH to inhibit specific TRH transcription/translation or a scrambled siRNA control in the left ventricle. Echocardiography was performed after 6 days since infarct to evaluate ventricular function and on the seventh day, animals were sacrificed and RNA extraction from hearts was assayed for quantification of gene expression by RT-PCR. For experiments in which the regional expression was determined, the infarct scar, and peri-infarct zone were dissected from the LV sample and treated separately, and similarly located regions of control hearts were also collected. As expected we observed a significant decrease in ejection fraction in infarcted compared to sham rats, and, in favor of our hypothesis, this decline was significantly lower in rats with the inhibition of the cardiac TRH system induced by siRNA-TRH, compared to animals injected with siRNA-Control. Consistently, we also found a significant increase in heart rate and end diastolic volume in the infarcted rats compared to sham rats, that was not observed in the rats treated with siRNA-TRH compared to rats injected with SiRNA-Control, which shows an improvement in ventricular function, an a decreased contractility and heart dilation. These results pointed out the benefit of inhibiting the system in this condition.As expected, we don?t observed changes in apoptotic indexes in the infarcted rats compared to sham rats regardless of treatment, probably because apoptosis is one of the earliest events in myocardial injury (early hours) and our experiment was performed at day 7 post-ligation focused in the post-ischemic remodeling.Related to gene expression, as expected, we found a significantly increase of myocardial TRH expression (p