Does antimiR-132 prevent heart failure development in a porcine model of pressure-overload-induced heart failure?
Inhibition of miR-132 via intracoronary injection of antimiR-132 may be a valid strategy to prevent heart failure progression in hypertrophic heart disease 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: ). 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.
“This is the first study worldwide to examine therapeutic miR-132 inhibition in a large animal model of nonischemic heart failure. We could demonstrate that miR-132 inhibition improves cardiac function and constitutes an efficient treatment option to prevent the conversion of physiologic to pathologic hypertrophy often observed in patients with heart failure of nonischemic origin. The study is adding further potential therapeutic options for our lead compound CDR132L.”
Hinkel et al. (Tue,) studied this question.