Regular Article VASCULAR BIOLOGY AngiomiR-126 expression and secretion from circulating CD34 and CD14 PBMCs: role for proangiogenic effects and alterations in type 2 diabetics

Key Points • AngiomiR-126 is secreted from circulating CD34 cells and acts as a signaling mechanism of pro-angiogenic effects on endothelial cells, which is impaired in diabetes. Several peripheral blood mononuclear cell (PBMC)–derived cell populations can promote angiogenesis, and differences in CD34 or CD14 surface expression have been used to separate PBMC subpopulations in this respect. AngiomiRs, microRNAs regulating angiogenesis, are key regulators of angiogenic processes. The present study examines differential angiomiR expression/secretion from CD34 /CD14 , CD34 / CD14 , CD34 /CD14 , and CD34 /CD14 PBMC subsets and their relevance for different proangiogenic properties. Notably, both circulating human CD34 /14 and CD34 /14 PBMC subsets and their supernatants exerted more potent proangiogenic effects compared with CD34 PBMC subsets. MiR-126 was identified as most differentially expressed angiomiR in CD34 compared with CD34 PBMC subsets, determined by miR-array and RT-PCR validation. Modulation of miR-126 by anti–miR-126 or miR-mimic-126 treatment resulted in significant loss or increase of proangiogenic effects of CD34 PBMCs. MiR-126 levels in supernatants of CD34 PBMC subsets were substantially higher compared with CD34 PBMC subsets. MiR-126 was secreted in microvesicles/ exosomes, and inhibition of their release impaired CD34 PBMCs proangiogenic effects. Notably, high-glucose treatment or diabetes reduced miR-126 levels of CD34 PBMCs, associated with impaired proangiogenic properties that could be rescued by miR-mimic-126 treatment. The present findings provide a novel molecular mechanism underlying increased proangiogenic effects of CD34 PBMCs, that is, angiomiR-126 expression/secretion. Moreover, an alteration of angiomiR-126 expression in CD34 PBMCs in diabetes provides a novel pathway causing impaired proangiogenic effects. (Blood. 2013;121(1):226-236)