Publication Date:
2009-05-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonauer, Angelika -- Carmona, Guillaume -- Iwasaki, Masayoshi -- Mione, Marina -- Koyanagi, Masamichi -- Fischer, Ariane -- Burchfield, Jana -- Fox, Henrik -- Doebele, Carmen -- Ohtani, Kisho -- Chavakis, Emmanouil -- Potente, Michael -- Tjwa, Marc -- Urbich, Carmen -- Zeiher, Andreas M -- Dimmeler, Stefanie -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1710-3. doi: 10.1126/science.1174381. Epub 2009 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19460962" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis/drug effects
;
Down-Regulation
;
Endothelial Cells/*metabolism
;
Gene Expression Profiling
;
Hindlimb/blood supply
;
Humans
;
Integrin alpha5/genetics/metabolism
;
Ischemia/drug therapy/metabolism/pathology/*physiopathology
;
Mice
;
Mice, Inbred C57BL
;
MicroRNAs/antagonists & inhibitors/*metabolism
;
Muscle, Skeletal/metabolism
;
Myocardial Infarction/metabolism/pathology/*physiopathology
;
Myocardium/metabolism
;
*Neovascularization, Physiologic
;
Oligoribonucleotides/pharmacology/therapeutic use
;
RNA, Messenger/genetics/metabolism
;
Regional Blood Flow
;
Up-Regulation
;
Ventricular Function, Left/drug effects
;
Zebrafish
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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