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

Aims 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 similar to 25 cluster in postnatal neovascularization and in regulation of the angiogenic properties of adult bone marrow-derived stromal cells. Methods and results To study the effect of miR-106b similar to 25 deletion on neovascularization, we used a miR-106b similar to 25 knockout (KO) mouse model. After inducing hindlimb ischaemia, we showed that vascularization in ischaemic mice devoid of miR-106b similar to 25 is impaired, as evident from the reduced blood flow on laser Doppler perfusion imaging. The miR-106b similar to 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 similar to 25 KO aortic rings is diminished. Conclusion These results show that the miR-106b similar to 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.