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


Mocharla, Pavani; Briand, Sylvie; Giannotti, Giovanna; Dörries, Carola; Jakob, Philipp; Paneni, Francesco; Lüscher, Thomas; Landmesser, Ulf (2013). AngiomiR-126 expression and secretion from circulating CD34+ and CD14+ PBMCs: role for pro-angiogenic effects and alterations in type-2 diabetics. Blood, 121(1):226-236.

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, have been identified as key regulators of angiogenic processes. The present study examines differential angiomiR-expression/secretion from CD34+/CD14+; CD34+/CD14-; CD34-/CD14+; CD34-/CD14- PBMC-subsets and their relevance for different pro-angiogenic properties. Notably, both circulating human CD34+/14+ and CD34+/14- PBMC-subsets and their supernatants exerted more potent pro-angiogenic effects as compared to CD34-PBMC-subsets. MiR-126 was identified as most differentially expressed angiomiR in CD34+ as compared to 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 pro-angiogenic effects of CD34+PBMCs. MiR-126 levels in supernatants of CD34+PBMC-subsets were substantially higher as compared to CD34- PBMC-subsets. MiR-126 was secreted in microvesicles/exosomes, and inhibition of their release impaired CD34+PBMCs pro-angiogenic effects. Notably, high-glucose treatment or diabetes reduced miR-126-levels of CD34+PBMCs, associated with impaired pro-angiogenic properties that could be rescued by miR-mimic-126 treatment. The present findings provide a novel molecular mechanism underlying increased pro-angiogenic effects of CD34+PBMC-subpopulations, i.e. angiomiR-126 expression/secretion. Moreover, an alteration of angiomiR-126-expression in CD34+PBMC in diabetes provides a new pathway causing impaired pro-angiogenic effects.

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, have been identified as key regulators of angiogenic processes. The present study examines differential angiomiR-expression/secretion from CD34+/CD14+; CD34+/CD14-; CD34-/CD14+; CD34-/CD14- PBMC-subsets and their relevance for different pro-angiogenic properties. Notably, both circulating human CD34+/14+ and CD34+/14- PBMC-subsets and their supernatants exerted more potent pro-angiogenic effects as compared to CD34-PBMC-subsets. MiR-126 was identified as most differentially expressed angiomiR in CD34+ as compared to 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 pro-angiogenic effects of CD34+PBMCs. MiR-126 levels in supernatants of CD34+PBMC-subsets were substantially higher as compared to CD34- PBMC-subsets. MiR-126 was secreted in microvesicles/exosomes, and inhibition of their release impaired CD34+PBMCs pro-angiogenic effects. Notably, high-glucose treatment or diabetes reduced miR-126-levels of CD34+PBMCs, associated with impaired pro-angiogenic properties that could be rescued by miR-mimic-126 treatment. The present findings provide a novel molecular mechanism underlying increased pro-angiogenic effects of CD34+PBMC-subpopulations, i.e. angiomiR-126 expression/secretion. Moreover, an alteration of angiomiR-126-expression in CD34+PBMC in diabetes provides a new pathway causing impaired pro-angiogenic effects.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:31 Jan 2013 14:55
Last Modified:05 Apr 2016 16:15
Publisher:American Society of Hematology
ISSN:0006-4971
Additional Information:This research was originally published in Blood. AngiomiR-126 expression and secretion from circulating CD34+ and CD14+ PBMCs: role for pro-angiogenic effects and alterations in type-2 diabetics. Copyright by the American Society of Hematology.
Publisher DOI:https://doi.org/10.1182/blood-2012-01-407106
PubMed ID:23144172

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