Abstract 67: miR-19 Deficiency Impairs Cardiac Repolarization in Zebrafish
The most common outcome of heart failure (HF) is sudden cardiac death which results mostly from prolonged action potential duration (APD) and arrhythmias. During the pathogenesis and progression of HF, a vast number of signaling pathways are altered. microRNAs are small noncoding RNAs that post-transcriptionally finetune gene expression. Interestingly, several microRNAs are dysregulated during HF, suggesting a potential involvement in the development and progression of the disease. Here, we identified miR-19 as an important regulator of heart function. Zebrafish lacking miR-19 developed severe bradycardia and reduced cardiac contractility. While the mammalian genome encodes for two isoforms of miR-19, zebrafish express four members (19a-d). We found that the reduction of miR-19b specifically is sufficient to cause bradycardia and reduced cardiac contractility. Imaging of ventricular APs from whole hearts revealed that APD is significantly prolonged and repolarization is impaired in miR-19b deficient zebrafish. By qRT-PCR experiments we showed that the expression of several cardiac ion channels is altered. Moreover, miR-19b deficiency results in increased sensitivity to an AV-Block, which is a characteristic feature of long QT-Syndrome in zebrafish. In conclusion, we identified miR-19b as a novel and essential modulator of the electrical activity of the heart and establish miR-19b as a potential candidate gene causative for human long QT syndrome.
Author Disclosures: A. Benz: None. H.A. Katus: None. D. Hassel: None.
- © 2015 by American Heart Association, Inc.