Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice
Patrick DM1, Montgomery RL2, Qi X1, Obad S3, Kauppinen S3,4, Hill JA5, van Rooij E2 and Olson EN1.
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
2miRagen Therapeutics, Boulder, Colorado, USA.
3Santaris Pharma, Hørsholm, Denmark.
4Copenhagen Institute of Technology, Aalborg University, Ballerup, Denmark.
5Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
MicroRNAs inhibit mRNA translation or promote mRNA degradation by binding complementary sequences in 3? untranslated regions of target mRNAs. MicroRNA-21 (miR-21) is upregulated in response to cardiac stress, and its inhibition by a cholesterol-modified antagomir has been reported to prevent cardiac hypertrophy and fibrosis in rodents in response to pressure overload. In contrast, we have shown here that miR-21–null mice are normal and, in response to a variety of cardiac stresses, display cardiac hypertrophy, fibrosis, upregulation of stress-responsive cardiac genes, and loss of cardiac contractility comparable to wildtype littermates. Similarly, inhibition of miR-21 through intravenous delivery of a locked nucleic acid–modified (LNA-modified) antimiR oligonucleotide also failed to block the remodeling response of the heart to stress. We therefore conclude that miR-21 is not essential for pathological cardiac remodeling.
http://www.jci.org/articles/view/43604
