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

Science. 2009 Jun 26;324(5935):1710-3. doi: 10.1126/science.1174381. Epub 2009 May 21.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antagomirs
  • Apoptosis / drug effects
  • Down-Regulation
  • Endothelial Cells / metabolism*
  • Gene Expression Profiling
  • Hindlimb / blood supply
  • Humans
  • Integrin alpha5 / genetics
  • Integrin alpha5 / metabolism
  • Ischemia / drug therapy
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Muscle, Skeletal / metabolism
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Myocardium / metabolism
  • Neovascularization, Physiologic*
  • Oligoribonucleotides / pharmacology
  • Oligoribonucleotides / therapeutic use
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Regional Blood Flow
  • Up-Regulation
  • Ventricular Function, Left / drug effects
  • Zebrafish

Substances

  • Antagomirs
  • Integrin alpha5
  • MIRN92 microRNA, human
  • MicroRNAs
  • Mirn92 microRNA, mouse
  • Oligoribonucleotides
  • RNA, Messenger
  • antagomir-92a