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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. and Carmona, G. and Iwasaki, M. and Mione, M. and Koyanagi, M. and Fischer, A. and Burchfield, J. and Fox, H. and Doebele, C. and Ohtani, K. and Chavakis, E. and Potente, M. and Tjwa, M. and Urbich, C. and 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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