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
Book Volume: 77
Pages Range: 2923-2935
Journal Issue: 23
DOI: 10.1016/j.jacc.2021.04.028
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.
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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