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

DM Patrick, RL Montgomery, X Qi… - The Journal of …, 2010 - Am Soc Clin Investig
DM Patrick, RL Montgomery, X Qi, S Obad, S Kauppinen, JA Hill, E Van Rooij, EN Olson
The Journal of clinical investigation, 2010Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation