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Published on: September 25, 2017
AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction
Rabea Hinkel1, Sandor Batkai2, Andrea Bähr3
1Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University of Munich, Munich, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany; Laboratory Animal Science Unit, German Primate Centre, Goettingen, Stiftung Tierärztliche Hochschule Hannover, Hannover, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), partner site Goettingen, Munich, Germany. Electronic address: https://twitter.com/Rabea08515954.
Insights
Inhibiting microRNA-132 (miR-132) effectively prevents heart failure progression in a novel porcine model of pressure-overload-induced cardiac hypertrophy. This approach reduces adverse cardiac remodeling and improves heart function, offering a potential treatment for nonischemic heart failure.
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Translational Medicine
Background:
- Pathological cardiac hypertrophy, driven by hypertension or aortic stenosis, causes adverse remodeling, dysfunction, and fibrosis, often leading to heart failure.
- Capillary rarefaction and interstitial fibrosis are key pathological features of advanced cardiac hypertrophy.
Purpose of the Study:
- To establish a novel porcine model of pressure-overload-induced heart failure.
- To investigate the therapeutic effect of inhibiting microRNA-132 (miR-132) on the progression of heart failure in this model.
Main Methods:
- A porcine model of pressure-overload heart failure was created using percutaneous aortic constriction.
- Inhibition of miR-132 was achieved using an antisense oligonucleotide (antimiR-132) delivered via intracoronary injection.
- Treatments were administered at the time of constriction induction and 28 days later, with assessments at 56 days.
Main Results:
- AntimiR-132 treatment significantly reduced cardiomyocyte size and improved global cardiac function (ejection fraction).
- Inhibition of miR-132 led to decreased interstitial fibrosis and increased cardiac capillary density compared to controls.
- The antimiR-132 treated hearts showed diminished pathological remodeling and improved functional parameters.
Conclusions:
- Inhibition of miR-132 is a viable strategy to prevent heart failure progression in hypertrophic heart disease.
- Targeting miR-132 may represent a novel therapeutic approach for heart failure of nonischemic origin.
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.
