TY - JOUR
T1 - AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction
AU - Hinkel, Rabea
AU - Batkai, Sandor
AU - Bähr, Andrea
AU - Bozoglu, Tarik
AU - Straub, Sarah
AU - Borchert, Tobias
AU - Viereck, Janika
AU - Howe, Andrea
AU - Hornaschewitz, Nadja
AU - Oberberger, Lisa
AU - Jurisch, Victoria
AU - Kozlik-Feldmann, Rainer
AU - Freudenthal, Franz
AU - Ziegler, Tilman
AU - Weber, Christian
AU - Sperandio, Markus
AU - Engelhardt, Stefan
AU - Laugwitz, Karl Ludwig
AU - Moretti, Alessandra
AU - Klymiuk, Nik
AU - Thum, Thomas
AU - Kupatt, Christian
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/6/15
Y1 - 2021/6/15
N2 - 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.
AB - 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.
KW - adverse cardiac remodeling
KW - antimiR-132
KW - cardiac hypertrophy
KW - heart failure
KW - microRNA-132
UR - http://www.scopus.com/inward/record.url?scp=85106951332&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2021.04.028
DO - 10.1016/j.jacc.2021.04.028
M3 - Article
C2 - 34112319
AN - SCOPUS:85106951332
SN - 0735-1097
VL - 77
SP - 2923
EP - 2935
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 23
ER -