Abstract
MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17approximately92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antagomirs
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Apoptosis / drug effects
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Down-Regulation
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Endothelial Cells / metabolism*
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Gene Expression Profiling
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Hindlimb / blood supply
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Humans
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Integrin alpha5 / genetics
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Integrin alpha5 / metabolism
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Ischemia / drug therapy
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Ischemia / metabolism
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Ischemia / pathology
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Ischemia / physiopathology*
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Mice
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Mice, Inbred C57BL
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / metabolism*
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Muscle, Skeletal / metabolism
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Myocardial Infarction / metabolism
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Myocardial Infarction / pathology
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Myocardial Infarction / physiopathology*
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Myocardium / metabolism
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Neovascularization, Physiologic*
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Oligoribonucleotides / pharmacology
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Oligoribonucleotides / therapeutic use
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Regional Blood Flow
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Up-Regulation
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Ventricular Function, Left / drug effects
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Zebrafish
Substances
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Antagomirs
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Integrin alpha5
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MIRN92 microRNA, human
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MicroRNAs
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Mirn92 microRNA, mouse
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Oligoribonucleotides
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RNA, Messenger
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antagomir-92a