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

Research output: Contribution to journalArticle

263 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)3912-3916
Number of pages5
JournalJournal of Clinical Investigation
Volume120
Issue number11
DOIs
StatePublished - Nov 1 2010

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MicroRNAs
Cardiomegaly
Fibrosis
RNA Stability
Protein Biosynthesis
3' Untranslated Regions
Oligonucleotides
Rodentia
Up-Regulation
Cholesterol
Pressure
Messenger RNA
mouse MIRN21 microRNA
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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

In: Journal of Clinical Investigation, Vol. 120, No. 11, 01.11.2010, p. 3912-3916.

Research output: Contribution to journalArticle

Patrick, DM, Montgomery, RL, Qi, X, Obad, S, Kauppinen, S, Hill, JA, Van Rooij, E & Olson, EN 2010, 'Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice', Journal of Clinical Investigation, vol. 120, no. 11, pp. 3912-3916. https://doi.org/10.1172/JCI43604
Patrick, David M. ; Montgomery, Rusty L. ; Qi, Xiaoxia ; Obad, Susanna ; Kauppinen, Sakari ; Hill, Joseph A ; Van Rooij, Eva ; Olson, Eric N. / Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. In: Journal of Clinical Investigation. 2010 ; Vol. 120, No. 11. pp. 3912-3916.
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