CARDIAC THYROTROPIN RELEASING HORMONE (TRH) INHIBITION ATTENUATES TISSUE DAMAGE AND IMPROVES VENTRICULAR FUNCTION AFTER MYOCARDIAL INFARCT IN RATS.

SCHUMAN, MARIANO LUIS; PERES DIAZ, LUDMILA; TOBLLI, JORGE E.; AISICOVICH, MAIA; INGALLINA, FERNANDO; LANDA, MARIA SILVINA; GARCIA, SILVIA INES

CABA

Congreso; XXIII Congreso Argentino de Hipertensión Arterial; 2016

SAHA

Heart injury induces ventricular remodeling. Particularlyacute myocardial infarction causes myocytes damage, reactive hypertrophy andinterstitial fibrosis in the infarcted area.We described TRH system hyperactivity in leftventricle (LV) hypertrophied SHR´s hearts. Indeed, TRH inhibition preventscardiac hypertrophy despite the severe hypertension suggesting its involvement (Schumanet al, 2011). We observed that LV TRH overexpression in normal rats induces featuresof the hypertrophic phenotype (Schuman et al 2014). Microarray studies revealed LV TRH increase after myocardialinfarction (Jin H. et al 2004), and added to our reports, we hypothesized thatLV TRH inhibition previous to infarct maneuver could attenuate cardiacremodeling damage.Adults Wistar males were infarcted by permanent anteriordescending coronary artery ligation simultaneously to 40ug  LV SiRNA injection against TRH or scrambled siRNA(control). At day 6 ventricular function evaluation was performed (echocardiography)and 24h later animals were sacrificed for heart gene expression quantitation (RT-PCR).Infarcted rats showed an expected significant decreasein ejection fraction and increases in heart rate and end diastolic volumecompared to sham group and according to our hypothesis, the animals in which LVTRH system was blocked all these changes were not observed pointing out that LVTRH inhibition prior to injury improves ventricular function and decreasescontractility and heart dilatation.As expected, we found a LV TRH overexpression in infarctedrats injected with siRNA-Control accompanied by significant increases in BNP,ANP, β-MHCand Collagen III and decreases in SERCA2 and α-actin expressions in harmony to heart tissue damageprofile including the contractility system.LV TRH inhibition which reduced significantly TRH geneexpression, blunted BNP, ANP, Collagen III and β-MHC increase and normalized the expression of SERCA2and α-actin.Theevaluation of the extracellular matrix (ECM) expansion in anatomopathologicalsamples of the hearts by Masson?s trichrome and Sirius red stains showed asignificant reduction in the increase of fibrosis in the peri-infarct area ofthe LV-TRH inhibited group compared with the infarcted control rats. In conclusion, we demonstrate for the first time, the participation of TRH in post-ischemic remodeling and point out that its inhibition provoke less expansion, attenuates the tissue damage and improves ventricular function after myocardial infarction.