Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Pavani Mocharla1,2,
  2. Sylvie Briand1,2,
  3. Giovanna Giannotti1,3,
  4. Carola Dörries1,2,
  5. Philipp Jakob1,2,
  6. Francesco Paneni1,4,
  7. Thomas Lüscher1,2, and
  8. Ulf Landmesser1,2
  1. 1Cardiovascular Centre, University Hospital Zurich and Cardiovascular Research, Institute of Physiology, University of Zurich, Zurich, Switzerland;
  2. 2Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland;
  3. 3Cardiac and Thoracic Department, University Hospital of Cisanello, Pisa, Italy; and
  4. 4Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli, Italy

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.

  • Submitted January 30, 2012.
  • Accepted June 24, 2012.
View Full Text