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

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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Tijsen AJ,van der Made I,van den Hoogenhof MM,Wijnen WJ,van Deel ED,de Groot NE,Alekseev S,Fluiter K,Schroen B,Goumans MJ,van der Velden J,Duncker DJ,Pinto YM,Creemers EE

doi

10.1093/cvr/cvu184

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

61-71

issue

1

eissn

0008-6363

issn

1755-3245

pii

cvu184

journal_volume

104

pub_type

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