MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.
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.
Bonauer
Angelika
A
Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Carmona
Guillaume
G
Iwasaki
Masayoshi
M
Mione
Marina
M
Koyanagi
Masamichi
M
Fischer
Ariane
A
Burchfield
Jana
J
Fox
Henrik
H
Doebele
Carmen
C
Ohtani
Kisho
K
Chavakis
Emmanouil
E
Potente
Michael
M
Tjwa
Marc
M
Urbich
Carmen
C
Zeiher
Andreas M
AM
Dimmeler
Stefanie
S
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
D000070416:Antagomirs; D039482:Integrin alpha5; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C541873:Mirn92 microRNA, mouse; D009843:Oligoribonucleotides; D012333:RNA, Messenger; C541876:antagomir-92a