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

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280 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 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.
Original languageEnglish
JournalJournal of Clinical Investigation
Volume120
Issue number11
Pages (from-to)3912-3916
Number of pages5
ISSN0021-9738
DOIs
Publication statusPublished - 1 Nov 2010

Keywords

  • Animals
  • Cardiomegaly
  • Hypertension
  • Mice
  • Mice, Knockout
  • MicroRNAs
  • Myocardial Contraction
  • Myocardium
  • Oligonucleotides, Antisense
  • Stress, Physiological
  • Ventricular Remodeling

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    Patrick, D. M., Montgomery, R. L., Qi, X., Obad, S., Kauppinen, S., Hill, J. A., van Rooij, E., & Olson, E. N. (2010). Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. Journal of Clinical Investigation, 120(11), 3912-3916. https://doi.org/10.1172/JCI43604