The microRNA-15 family inhibits the TGFβ-pathway in the heart.

Autor:	Tijsen AJ; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., van der Made I; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., van den Hoogenhof MM; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., Wijnen WJ; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., van Deel ED; Department of Cardiology, Thoraxcenter, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands., de Groot NE; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., Alekseev S; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., Fluiter K; Department of Genome Analysis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Schroen B; Department of Cardiology, Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands., Goumans MJ; Department of Molecular and Cell Biology, Centre of Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands., van der Velden J; Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands., Duncker DJ; Department of Cardiology, Thoraxcenter, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands., Pinto YM; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands., Creemers EE; Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands e.e.creemers@amc.uva.nl.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2014 Oct 01; Vol. 104 (1), pp. 61-71. Date of Electronic Publication: 2014 Aug 07.
DOI:	10.1093/cvr/cvu184
Abstrakt:	Aims: The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFβ-pathway is crucial for this remodelling. Here we tested the hypothesis that microRNAs in the overloaded heart regulate this remodelling process via inhibition of the TGFβ-pathway. Methods and Results: We show that the miRNA-15 family, which we found to be up-regulated in the overloaded heart in multiple species, inhibits the TGFβ-pathway by targeting of TGFBR1 and several other genes within this pathway directly or indirectly, including p38, SMAD3, SMAD7, and endoglin. Inhibition of miR-15b by subcutaneous injections of LNA-based antimiRs in C57BL/6 mice subjected to transverse aorta constriction aggravated fibrosis and to a lesser extent also hypertrophy. Conclusion: We identified the miR-15 family as a novel regulator of cardiac hypertrophy and fibrosis acting by inhibition of the TGFβ-pathway. (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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