Cardiac thyrotropin-releasing hormone (TRH) inhibition improves ventricular function and reduces hypertrophy and fibrosis after myocardial infarction in rats.

MARIANO L. SCHUMAN; PERES DIAZ LUDMILA; AISICOVICH, MAIA; FERNANDO INGALLINA; JORGE E TOBLLI; MARÍA S. LANDA; SILVIA INES GARCIA

JOURNAL OF CARDIAC FAILURE

CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS

Lugar: NY; Año: 2021

1071-9164

BackgroundCardiacthyrotropin-releasing hormone (TRH) is a tripeptide with still unknownfunctions. We demonstrated that the left ventricle (LV) TRH system ishyperactivated in spontaneously hypertensive rats and its inhibition preventedcardiac hypertrophy and fibrosis. Therefore,we evaluated whether in vivo cardiac TRH inhibition couldimprove myocardial function and attenuate ventricular remodeling in a rat modelof myocardial infarction (MI). Methods and ResultsInWistar rats, MI was induced by a permanent left anterior descending coronaryartery ligation. A coronary injection of a specific siRNA against TRH wassimultaneously applied. The control group received a scrambled siRNA.Cardiac remodeling variables were evaluated one week later. In MI rats, TRHinhibition decreased LV end-diastolic (1.049±0.102 vs. 1.339±0.102 ml, p<0.05), and end-systolic volumes(0.282±0.043 vs. 0.515±0.037 ml, p<0.001),and increased LV ejection fraction (71.89±2.80 vs. 65.69±2.85 %, p<0.05). Although both MI groupspresented similar infarct size, siRNA-the TRH treatment attenuated the cardiachypertrophy index and myocardial interstitial collagen deposition in the peri-infarctmyocardium. These effects were accompanied by attenuation in the rise of TGFβ,collagen I, and III and also the fetal genes (ANP, BNP, and βMHC) expression inthe peri-infarct region. Besides, the expression of Hif1α and VEGF significantlyincreased compared to all groups. ConclusionsCardiac TRH inhibition improves LV systolic functionand attenuates ventricular remodeling after MI. These novel findings supportthe idea that TRH inhibition may serve as a new therapeutic strategy againstthe progression of heart failure.