Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice.
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.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
David M
DM
Patrick
Rusty L
RL
Montgomery
Xiaoxia
X
Qi
Susanna
S
Obad
Sakari
S
Kauppinen
Joseph A
JA
Hill
Eva
E
van Rooij
Eric N
EN
Olson
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology*; D006973:Hypertension / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D020257:Ventricular Remodeling / Q000502:physiology*
C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense