title: MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.
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.
authors.affiliation: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bonauer
authors.forename: Guillaume
authors.initials: G
authors.lastname: Carmona
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Marina
authors.initials: M
authors.lastname: Mione
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Ariane
authors.initials: A
authors.lastname: Fischer
authors.forename: Jana
authors.initials: J
authors.lastname: Burchfield
authors.forename: Henrik
authors.initials: H
authors.lastname: Fox
authors.forename: Carmen
authors.initials: C
authors.lastname: Doebele
authors.forename: Kisho
authors.initials: K
authors.lastname: Ohtani
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Chavakis
authors.forename: Michael
authors.initials: M
authors.lastname: Potente
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Carmen
authors.initials: C
authors.lastname: Urbich
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000818:Animals; D000070416:Antagomirs; D017209:Apoptosis / Q000187:drug effects; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009843:Oligoribonucleotides / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects; D015027:Zebrafish
chemical_list: D000070416:Antagomirs; D039482:Integrin alpha5; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C541873:Mirn92 microRNA, mouse; D009843:Oligoribonucleotides; D012333:RNA, Messenger; C541876:antagomir-92a