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April 2020

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AntimiR-21 Prevents Myocardial Dysfunction in a Pig Model of Ischemia/Reperfusion Injury. JACC (2020), DZHK authors: Rabea Hinkel, Deepak Ramanujam, Katharina Klett, Christina Beck, Anne Dueck, Karl-Ludwig Laugwitz, Lars Maegdefessel, Christian Weber, Christian Kupatt, Stefan Engelhardt

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30% of patients with myocardial infarction develop heart failure, a condition characterized by adverse remodeling of the myocardium, including cardiac myocyte hypertrophy and fibrosis. Even under optimal medical treatment myocardial remodeling typically progresses and heart failure-related mortality rates remains high.

Novel therapeutic strategies are therefore urgently needed and interference with the action of specific microRNAs represent such a new therapeutic modality. MicroRNAs are small, non-coding, RNAs that are powerful regulators of gene expression and that have been shown to contribute to various cardiac diseases. They can effectively be inhibited with specific synthetic oligonucleotides, termed anti-miRs.

DZHK scientists from Pharmacology and Internal Medicine at Technische Universität München (TUM) teamed up and demonstrated that regional, intracoronary application of antimiR-21 prevented adverse remodeling by interfering with myocardial inflammation and fibrosis, significantly improving cardiac function. The entire study was conducted on pigs, a large animal model that is similar in anatomy and physiology to humans. Synthetic inhibitors of miRNA-21 (antimiR-21) are currently in phase II clinical testing in patients with renal fibrosis. The present study now suggests that catheter-based, regional application of LNA-antimiR-21 to the heart might offer a novel therapeutic option also to prevent the development of cardiac fibrosis and heart failure after acute myocardial infarction.