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

Authors

  • A. Bonauer
  • G. Carmona
  • M. Iwasaki
  • M. Mione
  • M. Koyanagi
  • A. Fischer
  • J. Burchfield
  • H. Fox
  • C. Doebele
  • K. Ohtani
  • E. Chavakis
  • M. Potente
  • M. Tjwa
  • C. Urbich
  • A.M. Zeiher
  • S. Dimmeler

Journal

  • Science

Citation

  • Science 324 (5935): 1710-1713

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.


DOI

doi:10.1126/science.1174381