| Autor: |
van Solingen, Coen, Seghers, Leonard, Bijkerk, Roel, Duijs, Jacques M.G.J., Roeten, Marko K., van Oeveren-Rietdijk, Annemarie M., Baelde, Hans J., Monge, Matthieu, Vos, Joost B., de Boer, Hetty C., Quax, Paul H.A., Rabelink, Ton J., Jan van Zonneveld, Anton |
| Předmět: |
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| Zdroj: |
Journal of Cellular & Molecular Medicine; Aug2009, Vol. 13 Issue 8a, p1577-1585, 9p, 2 Diagrams, 3 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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