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Science 324 (5935): 1710-1713

Copyright © 2009 by the American Association for the Advancement of Science

MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice

Angelika Bonauer,1 Guillaume Carmona,1 Masayoshi Iwasaki,1 Marina Mione,2 Masamichi Koyanagi,1 Ariane Fischer,1 Jana Burchfield,1 Henrik Fox,1,3 Carmen Doebele,1 Kisho Ohtani,1 Emmanouil Chavakis,1,3 Michael Potente,1,3 Marc Tjwa,4 Carmen Urbich,1 Andreas M. Zeiher,3 Stefanie Dimmeler1,*

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-17~92 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.

1 Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
2 Italian Foundation for Cancer Research Institute of Molecular Oncology Foundation, 02139 Milan, Italy.
3 Division of Cardiology, Department of Medicine III, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
4 Leibniz AG, Institute for Cardiovascular Regeneration, Goethe-University Frankfurt, 60590 Frankfurt, Germany.

* To whom correspondence should be addressed. E-mail: dimmeler{at}em.uni-frankfurt.de


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