AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction.
Animals
Antagomirs
/ administration & dosage
Aorta, Thoracic
/ surgery
Aortic Diseases
/ complications
Cardiomegaly
/ complications
Constriction
Constriction, Pathologic
/ complications
Coronary Vessels
Disease Models, Animal
Heart Failure
/ etiology
Injections, Intra-Arterial
MicroRNAs
/ antagonists & inhibitors
Stents
/ adverse effects
Swine
Treatment Outcome
Ventricular Remodeling
/ drug effects
adverse cardiac remodeling
antimiR-132
cardiac hypertrophy
heart failure
microRNA-132
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
15 06 2021
15 06 2021
Historique:
received:
05
03
2021
revised:
01
04
2021
accepted:
09
04
2021
entrez:
11
6
2021
pubmed:
12
6
2021
medline:
24
11
2021
Statut:
ppublish
Résumé
Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure. This study aimed to establish a novel porcine model of pressure-overload-induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model. This study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28. At d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm The inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin.
Sections du résumé
BACKGROUND
Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure.
OBJECTIVES
This study aimed to establish a novel porcine model of pressure-overload-induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model.
METHODS
This study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28.
RESULTS
At d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm
CONCLUSIONS
The inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin.
Identifiants
pubmed: 34112319
pii: S0735-1097(21)04781-1
doi: 10.1016/j.jacc.2021.04.028
pii:
doi:
Substances chimiques
Antagomirs
0
MIRN132 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2923-2935Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
FUNDING SUPPORT AND AUTHOR DISCLOSURES This study was supported by the Deutsches Zentrum für Herz-Kreislauf-Forschung (German Centre for Cardiovascular Research) (to Drs. Hinkel, Weber, Engelhardt, Laugwitz, Moretti, and Kupatt) and, with regard to model development, by the Deutsche Forschungsgemeinschaft (German Research Foundation) (TRR 267 to Drs. Thum, Weber, Engelhardt, Laugwitz, and Kupatt.; and KFO311 to Dr. Thum.). Drs. Baktai and Thum are founders of Cardior Pharmaceuticals GmbH and hold shares. Dr. Thum filed and licensed patents in the field of noncoding ribonucleic acids including miR-132. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.