Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice
David M. Patrick, … , Eva van Rooij, Eric N. Olson
David M. Patrick, … , Eva van Rooij, Eric N. Olson
Published November 1, 2010; First published October 18, 2010
Citation Information: J Clin Invest. 2010;120(11):3912-3916. https://doi.org/10.1172/JCI43604.
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Category: Brief Report

Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice

Abstract

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 wild-type 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.

Authors

David M. Patrick, Rusty L. Montgomery, Xiaoxia Qi, Susanna Obad, Sakari Kauppinen, Joseph A. Hill, Eva van Rooij, Eric N. Olson

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Figure 1

miR-21 is not required for cardiac hypertrophy or fibrosis in response to stress.

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miR-21 is not required for cardiac hypertrophy or fibrosis in response t...
(A) Trichrome staining on cardiac sections of WT and Mir21–/– (KO) animals after TAC, transgenic expression of calcineurin, chronic Ang II infusion, or MI, as indicated. Histological analysis shows that miR-21 deletion has no effect on cardiac remodeling in response to stress, based on cardiac hypertrophy and fibrosis. (B) HW/BW ratios of mice of the indicated genotypes in response to the indicated stresses. HW/BW data shown for TAC experiments represent n = 9 for WT sham, n = 10 for KO sham, n = 14 for WT TAC, and n = 13 for KO TAC. HW/BW data shown for calcineurin overexpression represent n = 4 WT non-Tg, n = 3 KO non-Tg, n = 4 WT Tg, and n = 3 KO Tg. HW/BW data shown for Ang II infusion represent n = 9 WT saline, n = 8 KO saline, n = 11 WT Ang II, and n = 7 KO Ang II. (C) Detection of miR-21 expression in hearts of mice of the indicated genotypes in response to the indicated stresses by Northern blot analysis. RNU6B was detected as loading control. CNA, calcineurin. (D) Trichrome staining of hearts of the indicated genotypes 3 weeks following TAC surgery. Scale bars: 100 μm.