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MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice

Item Type:Article
Title:MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice
Creators Name:Bonauer, A., Carmona, G., Iwasaki, M., Mione, M., Koyanagi, M., Fischer, A., Burchfield, J., Fox, H., Doebele, C., Ohtani, K., Chavakis, E., Potente, M., Tjwa, M., Urbich, C., Zeiher, A.M. and Dimmeler, S.
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.
Keywords:Antagomirs, Apoptosis, Down-Regulation, Endothelial Cells, Gene Expression, Hindlimb, Inbred C57BL Mice, Integrin alpha5, Ischemia, Left Ventricular Function, Messenger RNA, MicroRNAs, Myocardial Infarction, Myocardium, Oligoribonucleotides, Physiologic Neovascularization, Regional Blood Flow, Skeletal Muscle, Up-Regulation, Animals, Mice, Zebrafish
Source:Science
ISSN:0036-8075
Publisher:American Association for the Advancement of Science
Volume:324
Number:5935
Page Range:1710-1713
Date:26 June 2009
Official Publication:https://doi.org/10.1126/science.1174381
PubMed:View item in PubMed

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