Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice
David M. Patrick, Rusty L. Montgomery, Xiaoxia Qi, Susanna Obad, Sakari Kauppinen, Joseph A. Hill, Eva van Rooij, Eric N. Olson
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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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 2

miR-21 deletion does not alter the expression of cardiac stress markers.

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miR-21 deletion does not alter the expression of cardiac stress markers....
(A) Quantitative real-time PCR analysis for hearts of the indicated genotypes in response to the indicated stresses shows no effect on cardiac gene expression during stress in the absence of miR-21. Gene expression data shown for TAC experiments represent n = 6 for WT sham, n = 6 for KO sham, n = 10 for WT TAC, and n = 10 for KO TAC. Data shown for calcineurin overexpression represent n = 3 WT non-Tg, n = 3 KO non-Tg, n = 3 WT Tg, and n = 3 KO Tg. Data shown for Ang II infusion represent n = 3 WT saline, n = 3 KO saline, n = 4 WT Ang II, and n = 3 KO Ang II. (B) Western blot analysis indicates a comparable stress-induced increase in phospho-ERK for both WT and Mir21–/– (KO) hearts in response to TAC.