AngiomiR-126 expression and secretion from circulating CD34+ and CD14+ PBMCs: Role for proangiogenic effects and alterations in type 2 diabetics

Abstract

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. © 2013 by The American Society of Hematology.