Role of endothelial microRNA-23 clusters in angiogenesis in vivo.

The capillary network is distributed throughout the body, and its reconstruction is induced under various pathophysiological conditions. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression via post-transcriptional mechanisms and are involved in many biological functions including angiogenesis. Previous studies have shown that each miRNA of the miR-23 cluster, composed of the miR-23a cluster (miR-23a~27a~24-2) and miR-23b cluster (miR-23b~27b~24-2), regulates angiogenesis in vitro. However, the role of the endothelium-specific miR-23 cluster, located within a single transcription unit, in angiogenesis in vivo has not been elucidated. In the present study, we generated vascular endothelial cell (EC)-specific miR-23 double knockout mice (DKO) and demonstrated sprouting angiogenesis under various conditions, including voluntary running exercise, skin wound healing, and EC sprouting from aorta explants. Here, we demonstrated that EC-specific miR-23 DKO mice were viable and fertile, with no gross abnormalities observed in the pups or adults. The capillary number was increased in the muscles of these DKO mice in response to 2 weeks of voluntary running. Furthermore, we did not observe any abnormalities in skin wound closure or EC sprouting from aortic ring explants in EC-specific miR-23 DKO mice. Our results suggest that endothelial miR-23 clusters are dispensable for embryonic development and postnatal angiogenesis in vivo.