The 106b∼25 microRNA cluster is essential for neovascularization after hindlimb ischaemia in mice

MicroRNAs (miRNAs, miR) are endogenous short RNA sequences that regulate a wide range of physiological and pathophysiological processes. Several miRNAs control the formation of new blood vessels either by increasing or by inhibiting angiogenesis. Here, we investigated the possible role of the miR-10...

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Published in:European heart journal 2014-12, Vol.35 (45), p.3212-3223
Main Authors: Semo, Jonathan, Sharir, Rinat, Afek, Arnon, Avivi, Camila, Barshack, Iris, Maysel-Auslender, Sofia, Krelin, Yakov, Kain, David, Entin-Meer, Michal, Keren, Gad, George, Jacob
Format: Article
Language:English
Subjects:
AC133 Antigen
Animals
Antigens, CD - metabolism
Antigens, Ly - metabolism
Aorta - physiology
Apoptosis - physiology
Blood Flow Velocity - physiology
Bone Marrow Cells - physiology
Cell Movement - physiology
Cell Proliferation - physiology
Cell Survival - physiology
Endothelial Cells - physiology
Female
Glycoproteins - metabolism
Hindlimb - blood supply
Ischemia - physiopathology
Membrane Proteins - metabolism
Mice, Knockout
MicroRNAs - metabolism
MicroRNAs - physiology
Neovascularization, Physiologic - physiology
Paracrine Communication - physiology
Peptides - metabolism
Proto-Oncogene Proteins c-kit - metabolism
PTEN Phosphohydrolase - metabolism
Stromal Cells - physiology
Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Summary:MicroRNAs (miRNAs, miR) are endogenous short RNA sequences that regulate a wide range of physiological and pathophysiological processes. Several miRNAs control the formation of new blood vessels either by increasing or by inhibiting angiogenesis. Here, we investigated the possible role of the miR-106b∼25 cluster in postnatal neovascularization and in regulation of the angiogenic properties of adult bone marrow-derived stromal cells. To study the effect of miR-106b∼25 deletion on neovascularization, we used a miR-106b∼25 knockout (KO) mouse model. After inducing hindlimb ischaemia, we showed that vascularization in ischaemic mice devoid of miR-106b∼25 is impaired, as evident from the reduced blood flow on laser Doppler perfusion imaging. The miR-106b∼25 cluster was also shown here to be an essential player in the proper functioning of bone marrow-derived stromal cells through its regulation of apoptosis, matrigel tube formation capacity, cytokine secretion, and expression of the stem-cell marker Sca-1. In addition, we showed that capillary sprouting from miR-106b∼25 KO aortic rings is diminished. These results show that the miR-106b∼25 cluster regulates post-ischaemic neovascularization in mice, and that it does so in part by regulating the function of angiogenic bone marrow-derived stromal cells and of endothelial cells.
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/eht041