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Inhibition of the 14q32 microRNAs, miR-329-3p and miR-495-3p, improves post-ischemic neovascularization. Cold-inducible RNA-binding protein (<i>CIRBP</i>) facilitates maturation of these microRNAs. We hypothesized that <i>CIRBP</i> deficiency improves post-ischemic angiogenesis via downregulation of 14q32 microRNA expression. We investigated these regulatory mechanisms both in vitro and in vivo. We induced hindlimb ischemia in <i>Cirp^−/−</i> and C57Bl/6-J mice, monitored blood flow recovery with laser Doppler perfusion imaging, and assessed neovascularization via immunohistochemistry. Post-ischemic angiogenesis was enhanced in <i>Cirp^−/−</i> mice by 34.3% with no effects on arteriogenesis. In vivo at day 7, miR-329-3p and miR-495-3p expression were downregulated in <i>Cirp^−/−</i> mice by 40.6% and 36.2%. In HUVECs, <i>CIRBP</i> expression was upregulated under hypothermia, while miR-329-3p and miR-495-3p expression remained unaffected. siRNA-mediated <i>CIRBP</i> knockdown led to the downregulation of <i>CIRBP</i>-splice-variant-1 (<i>CIRBP-SV1</i>), <i>CIRBP</i> antisense long noncoding RNA (lncRNA-<i>CIRBP</i>-AS1), and miR-495-3p with no effects on the expression of <i>CIRBP-SV2-4</i> or miR-329-3p. siRNA-mediated <i>CIRBP</i> knockdown improved HUVEC migration and tube formation. SiRNA-mediated lncRNA-<i>CIRBP</i>-AS1 knockdown had similar long-term effects. After short incubation times, however, only <i>CIRBP</i> knockdown affected angiogenesis, indicating that the effects of lncRNA-<i>CIRBP</i>-AS1 knockdown were secondary to <i>CIRBP-SV1</i> downregulation. <i>CIRBP</i> is a negative regulator of angiogenesis in vitro and in vivo and acts, at least in part, through the regulation of miR-329-3p and miR-495-3p.