| Autor: |
Solingen, C. van, Seghers, L., Bijkerk, R., Duijs, J.M.G.J., Roeten, M.K., Oeveren van - Rietdijk, A.M., Baelde, H.J., Monge, M., Vos, J.B., Boer, H.C. de, Quax, P.H.A., Rabelink, T.J., Zonneveld, A.J. van |
| Přispěvatelé: |
TNO Kwaliteit van Leven |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
Journal of Cellular and Molecular Medicine, 8 A, 13, 1577-1585 |
| Popis: |
MicroRNAs are negative regulators of gene expression that play a key role in cell-type specific differentiation and modulation of cell function and have been proposed to be involved in neovascularization. Previously, using an extensive cloning and sequencing approach, we identified miR-126 to be specifically and highly expressed in human endothelial cells (EC). Here, we demonstrate EC-specific expression of miR-126 in capillaries and the larger vessels in vivo. We therefore explored the potential role of miR-126 in arteriogenesis and angiogenesis. Using miR-reporter constructs, we show that miR-126 is functionally active in EC in vitro and that it could be specifically repressed using antagomirs specifically targeting miR-126. To study the consequences of miR-126 silencing on vascular regeneration, mice were injected with a single dose of antagomir-126 or a control 'scramblemir' and exposed to ischemia of the left hindlimb by ligation of the femoral artery. Although miR-126 was effectively silenced in mice treated with a single, high dose (HD) of antagomir-126, laser Doppler perfusion imaging did not show effects on blood flow recovery. In contrast, quantification of the capillary density in the gastrocnemius muscle revealed that mice treated with a HD of antagomir-126 had a markedly reduced angiogenic response. Aortic explant cultures of the mice confirmed the role of miR-126 in angiogenesis. Our data demonstrate a facilitary function for miR-126 in ischemia-induced angiogenesis and show the efficacy and specificity of antagomir-induced silencing of EC-specific microRNAs in vivo. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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