Hypoxia-induced miR-210 modulates inflammatory response and fibrosis upon acute peripheral ischemia

Abstract Introduction We previously demonstrated in mouse models of peripheral and heart ischemia that miR-210 is necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase following ischemic damage. Aim To clarify the role of inflammatory cells in miR-210-induced angiogenesis. Methods and results In a mouse model of acute limb ischemia, miR-210 loss-of-function was obtained by administration of complementary anti-miR-210 LNA oligonucleotides (anti-210), while doxycycline-inducible miR-210 transgenic mice (Tg210) were used for gain-of-function experiments. Transcriptomic and gene ontology analysis in ischemic gastrocnemius muscles upon miR-210 blocking displayed an enrichment of categories related not only to angiogenesis, but also to inflammation, suggesting that miR-210 decrease prompted a pro-inflammatory and anti-regenerative response. Accordingly, immunofluorescence staining of ischemic muscles of anti-210 treated mice, showed an increased presence of granulocytes (Scr = 28±7, anti-210 = 108±17 cells/mm2, p