Inhibition of miR-208b improves cardiac function in titin-based dilated cardiomyopathy
Background: Dilated cardiomyopathy (DCM) is the result of maladaptive cardiac remodeling, which involves microRNA regulation. In turn, microRNAs can contribute to the remodeling process by post-transcriptional modulation of gene expression networks. The exact role of microRNAs in the pathogenesis of...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
International journal of cardiology
Year: 2016, Volume: 230, Pages: 634-641 |
| ISSN: | 1874-1754 |
| DOI: | 10.1016/j.ijcard.2016.12.171 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.ijcard.2016.12.171 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0167527316348227 
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| Author Notes: | Qifeng Zhou, Sonja Schötterl, Daniel Backes, Eva Brunner, Julia Kelley Hahn, Elena Ionesi, Parwez Aidery, Carsten Sticht, Siegfried Labeit, Reinhard Kandolf, Meinrad Gawaz and Michael Gramlich |
| Summary: | Background: Dilated cardiomyopathy (DCM) is the result of maladaptive cardiac remodeling, which involves microRNA regulation. In turn, microRNAs can contribute to the remodeling process by post-transcriptional modulation of gene expression networks. The exact role of microRNAs in the pathogenesis of DCM is largely unknown. Here, we used an inducible DCM mouse model that carries a human truncation mutation in the sarcomeric protein titin to dissect microRNA pathways in DCM development. Methods and results: MicroRNA microarray studies revealed up-regulation of microRNA-208b in the myocardium of DCM mice and DCM patients (p<0.05 compared to controls). In order to investigate the effect of microRNA-208b on cardiac remodeling, loss-of-function and gain-of-function studies were performed by repetitive injections of LNA-modified microRNA-208b mimics and antimiR-208b. MiR-208b overexpression resulted in cardiac hypertrophy, whereas miR-208b antagonisation prevented transition of adaptive to maladaptive remodeling in the DCM mouse model. In vitro studies identified several pro-hypertrophic transcription factors as potential targets of miR-208b, suggesting that microRNA-208b plays an important role in cardiac development and growth. MiR-208b was also upregulated in DCM patients, but not in heart failure patients due to ischemic heart disease or myocarditis. Conclusion: Our data suggests that miR-208b is involved in the remodeling process and pathogenesis of DCM by post-transcriptional gene expression modulation. MicroRNA-208b might be a novel therapeutic target for DCM. |
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| Item Description: | Available online 28 December 2016 Gesehen am 09.08.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1874-1754 |
| DOI: | 10.1016/j.ijcard.2016.12.171 |