Cardiac Thyrotropin Releasing Hormone (TRH) Inhibition attenuates the post-ischemic damage and improves ventricular function after myocardial infarction in rats

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

Buenos Aires

Congreso; ISHR XXII WORLD CONGRESS; 2016

International Society for Heart Research

Heart injury induces ventricular remodeling.Particularly acute myocardial infarction causes myocytes damage, reactivehypertrophy and interstitial 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(Schuman et al, 2011). We observed that LV TRH overexpression in normal ratsinduces features of the hypertrophic phenotype (Schuman et al 2014). Microarray studies revealed LV TRH increase aftermyocardial infarction (Jin H. et al 2004), and added to our reports, wehypothesized that LV TRH inhibition previous to infarct maneuver couldattenuate cardiac remodeling damage.Adults Wistar males were infarcted by permanentanterior descending coronary artery ligation simultaneously to 40ug  LV SiRNA injection against TRH or scrambledsiRNA (control). At day 6 ventricular function evaluation was performed(echocardiography) and 24h later animals were sacrificed for heart geneexpression 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 ininfarcted rats injected with siRNA-Control accompanied by significant increasesin BNP, ANP, β-MHC andCollagen III and decreases in SERCA2 and α-actin expressions in harmony to heart tissuedamage profile 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 ofSERCA2 and α-actin.These novels results demonstrate the participation ofTRH in post-ischemic remodeling and reveal that its inhibition attenuates the damage and improves ventricular function.