| Title: |
AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction. |
| Authors: |
Hinkel, Rabea; Batkai, Sandor; Bähr, Andrea; Bozoglu, Tarik; Straub, Sarah; Borchert, Tobias; Viereck, Janika; Howe, Andrea; Hornaschewitz, Nadja; Oberberger, Lisa; Jurisch, Victoria; Kozlik-Feldmann, Rainer; Freudenthal, Franz; Ziegler, Tilman; Weber, Christian; Sperandio, Markus; Engelhardt, Stefan; Laugwitz, Karl Ludwig; Moretti, Alessandra; Klymiuk, Nik; Thum, Thomas; Kupatt, Christian |
| Contributors: |
Arbeitsgruppe Tissue Engineering und Regenerative Medizin; Institut für Pharmakologie und Toxikologie; Klinik und Poliklinik für Innere Medizin I, Kardiologie |
| Publication Year: |
2021 |
| Collection: |
Munich University of Technology (TUM): mediaTUM |
| Subject Terms: |
info:eu-repo/classification/ddc |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
https://mediatum.ub.tum.de/1624309 |
| DOI: |
10.1016/j.jacc.2021.04.028 |
| Availability: |
https://mediatum.ub.tum.de/1624309; https://doi.org/10.1016/j.jacc.2021.04.028 |
| Rights: |
info:eu-repo/semantics/restrictedAccess |
| Accession Number: |
edsbas.CE3CD96B |
| Database: |
BASE |