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

LUDMILA S PERES DIAZ; FERNANDO INGALLINA; MARIANO L SCHUMAN; MAIA AISICOVICH; SILVIA I GARCÍA; JORGE E TOBLLI; MARIA S LANDA

Buenos Aires

Congreso; XXIII Congreso de la Sociedad Argentina de Hipertensión Arterial.; 2016

Sociedad Argentina de Hipertensión Arterial-International Society of Hypertension

Heart injury induces ventricular remodeling. Particularly acute myocardial infarction causes myocytes damage, reactive hypertrophy and interstitial fibrosis in the infarcted area.We described TRH system hyperactivity in left ventricle (LV) hypertrophied SHR´s hearts. Indeed, TRH inhibition prevents cardiac hypertrophy despite the severe hypertension suggesting its involvement (Schuman et al, 2011). We observed that LV TRH overexpression in normal rats induces features of the hypertrophic phenotype (Schuman et al 2014). Microarray studies revealed LV TRH increase after myocardial infarction (Jin H. et al 2004), and added to our reports, we hypothesized that LV TRH inhibition previous to infarct maneuver could attenuate cardiac remodeling damage.Adults Wistar males were infarcted by permanent anterior descending 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 decrease in ejection fraction and increases in heart rate and end diastolic volume compared to sham group and according to our hypothesis, the animals in which LV TRH system was blocked all these changes were not observed pointing out that LV TRH inhibition prior to injury improves ventricular function and decreases contractility and heart dilatation.As expected, we found a LV TRH overexpression in infarcted rats injected with siRNA-Control accompanied by significant increases in BNP, ANP, β-MHC and Collagen III and decreases in SERCA2 and α-actin expressions in harmony to heart tissue damage profile including the contractility system.LV TRH inhibition which reduced significantly TRH gene expression, blunted BNP, ANP, Collagen III and β-MHC increase and normalized the expression of SERCA2 and α-actin.The evaluation of the extracellular matrix (ECM) expansion in anatomopathological samples of the hearts by Masson?s trichrome and Sirius red stains showed a significant reduction in the increase of fibrosis in the peri-infarct area of the 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.