AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction
Hinkel R, Batkai S, Baehr A, Bozoglu T, Straub S, Borchert T, Viereck J, Howe A, Hornaschewitz N, Oberberger L, Jurisch V, Kozlik-Feldmann R, Freudenthal F, Ziegler T, Weber C, Sperandio M, Engelhardt S, Laugwitz KL, Moretti A, Klymiuk N, Thum T, Kupatt C (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 77
Pages Range: 2923-2935
Journal Issue: 23
DOI: 10.1016/j.jacc.2021.04.028
Abstract
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 μm2 in untreated hypertrophic hearts) and improved global cardiac function (ejection fraction 48.9 ± 1.0% vs. 36.1 ± 1.7% in control hearts). Moreover, at d56 antimiR-132-treated hearts displayed less increase of interstitial fibrosis compared with sham-operated hearts (Δsham 1.8 ± 0.5%) than control hearts (Δsham 10.8 ± 0.6%). Of note, cardiac platelet and endothelial cell adhesion molecule 1+ capillary density was higher in the antimiR-132–treated hearts (647 ± 20 cells/mm2) compared with in the control group (485 ± 23 cells/mm2). 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.
Involved external institutions
Technische Universität München (TUM)
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Cardior Pharmaceuticals GmbH
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK e.V.)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Germany (DE)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Cardior Pharmaceuticals GmbH
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK e.V.)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
How to cite
APA:
Hinkel, R., Batkai, S., Baehr, A., Bozoglu, T., Straub, S., Borchert, T.,... Kupatt, C. (2021). AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction. Journal of the American College of Cardiology, 77(23), 2923-2935. https://doi.org/10.1016/j.jacc.2021.04.028
MLA:
Hinkel, Rabea, et al. "AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction." Journal of the American College of Cardiology 77.23 (2021): 2923-2935.
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