Cardiac Thyrotropin-releasing Hormone Inhibition Improves Ventricular Function and Reduces Hypertrophy and Fibrosis After Myocardial Infarction in Rats.

Autor: Schuman ML; University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Cardiology, Ciudad Autónoma de Buenos Aires, Argentina., Peres Diaz LS; University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Cardiology, Ciudad Autónoma de Buenos Aires, Argentina., Aisicovich M; University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Cardiology, Ciudad Autónoma de Buenos Aires, Argentina., Ingallina F; University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina; University of Buenos Aires (UBA), School of Medicine, Institute of Medical Research 'Alfredo Lanari,' Department of Cardiology, Ciudad Autonoma de Buenos Aires, Argentina., Toblli JE; Laboratory of Experimental Medicine, Hospital Alemán, Ciudad Autonoma de Buenos Aires, Argentina., Landa MS; University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Cardiology, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Ciudad Autonoma de Buenos Aires, Argentina., García SI; University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Cardiology, Ciudad Autónoma de Buenos Aires, Argentina; Laboratory of Experimental Medicine, Hospital Alemán, Ciudad Autonoma de Buenos Aires, Argentina. Electronic address: garcia.silvia@lanari.uba.ar.
Jazyk: angličtina
Zdroj: Journal of cardiac failure [J Card Fail] 2021 Jul; Vol. 27 (7), pp. 796-807. Date of Electronic Publication: 2021 Apr 15.
DOI: 10.1016/j.cardfail.2021.04.003
Abstrakt: Background: Cardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI).
Methods and Results: In Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific small interfering RNA against TRH was applied simultaneously. The control group received a scrambled small interfering RNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049 ± 0.102 mL vs 1.339 ± 0.102 mL, P < .05), and end-systolic volumes (0.282 ± 0.043 mL vs 0.515 ± 0.037 mL, P < .001), and increased LV ejection fraction (71.89 ± 2.80% vs 65.69 ± 2.85%, P < .05). Although both MI groups presented similar infarct size, small interfering RNA against TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of transforming growth factor-β, collagen I, and collagen III, as well as the fetal genes (atrial natriuretic peptide, B-type natriuretic peptide, and beta myosin heavy chain) expression in the peri-infarct region. In addition, the expression of Hif1α and vascular endothelial growth factor significantly increased compared with all groups.
Conclusions: Cardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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