The microRNA-15 family inhibits the TGFβ-pathway in the heart. (7th August 2014)

• Record Type: Journal Article
• Authors: Tijsen, Anke J.; van der Made, Ingeborg; van den Hoogenhof, Maarten M.; Wijnen, Wino J.; van Deel, Elza D.; de Groot, Nina E.; Alekseev, Sergey; Fluiter, Kees; Schroen, Blanche; Goumans, Marie-José; van der Velden, Jolanda; Duncker, Dirk J.; Pinto, Yigal M.; Creemers, Esther E.
• Is Part Of: Cardiovascular research. Volume 104:Number 1(2015)
• Page Start: 61
• Page End: 71
• Publication Date: 2014-08-07
• Subjects: Fibrosis -- Hypertrophy -- miRNA-15 family -- TGFβ-pathway; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvu184
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: 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.