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 language | English |
---|---|
Journal | Journal of Clinical Investigation |
Volume | 120 |
Issue number | 11 |
Pages (from-to) | 3912-3916 |
Number of pages | 5 |
ISSN | 0021-9738 |
DOIs | |
Publication status | Published - 1 Nov 2010 |
Keywords
- Animals
- Cardiomegaly
- Hypertension
- Mice
- Mice, Knockout
- MicroRNAs
- Myocardial Contraction
- Myocardium
- Oligonucleotides, Antisense
- Stress, Physiological
- Ventricular Remodeling