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

被引:1023
作者
Bonauer, Angelika [1 ]
Carmona, Guillaume [1 ]
Iwasaki, Masayoshi [1 ]
Mione, Marina [2 ]
Koyanagi, Masamichi [1 ]
Fischer, Ariane [1 ]
Burchfield, Jana [1 ]
Fox, Henrik [1 ,3 ]
Doebele, Carmen [1 ]
Ohtani, Kisho [1 ]
Chavakis, Emmanouil [1 ,3 ]
Potente, Michael [1 ,3 ]
Tjwa, Marc [4 ]
Urbich, Carmen [1 ]
Zeiher, Andreas M. [3 ]
Dimmeler, Stefanie [1 ]
机构
[1] Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany
[2] Mol Oncol Fdn, Italian Fdn Canc Res Inst, I-02139 Milan, Italy
[3] Univ Frankfurt, Dept Med 3, Div Cardiol, D-60590 Frankfurt, Germany
[4] Univ Frankfurt, Leibniz AG, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany
基金
欧洲研究理事会;
关键词
ENDOTHELIAL-CELL MIGRATION; VASCULAR INTEGRITY; EXPRESSION; DICER; FIBRONECTIN; POLYCISTRON; ALPHA(5); GENE;
D O I
10.1126/science.1174381
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-17 similar to 92 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.
引用
收藏
页码:1710 / 1713
页数:4
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