Cold-Inducible RNA-Binding Protein but Not Its Antisense lncRNA Is a Direct Negative Regulator of Angiogenesis In Vitro and In Vivo via Regulation of the 14q32 angiomiRs-microRNA-329-3p and microRNA-495-3p.

Inhibition of the 14q32 microRNAs, miR-329-3p and miR-495-3p, improves post-ischemic neovascularization. Cold-inducible RNA-binding protein () facilitates maturation of these microRNAs. We hypothesized that 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 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 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 mice by 40.6% and 36.2%. In HUVECs, expression was upregulated under hypothermia, while miR-329-3p and miR-495-3p expression remained unaffected. siRNA-mediated knockdown led to the downregulation of -splice-variant-1 (), antisense long noncoding RNA (lncRNA--AS1), and miR-495-3p with no effects on the expression of or miR-329-3p. siRNA-mediated knockdown improved HUVEC migration and tube formation. SiRNA-mediated lncRNA--AS1 knockdown had similar long-term effects. After short incubation times, however, only knockdown affected angiogenesis, indicating that the effects of lncRNA--AS1 knockdown were secondary to downregulation. 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.