title: 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.
authors.affiliation: Cardiovascular Centre, University Hospital Zurich and Cardiovascular Research, Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Pavani
authors.initials: P
authors.lastname: Mocharla
authors.forename: Sylvie
authors.initials: S
authors.lastname: Briand
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giannotti
authors.forename: Carola
authors.initials: C
authors.lastname: Dörries
authors.forename: Philipp
authors.initials: P
authors.lastname: Jakob
authors.forename: Francesco
authors.initials: F
authors.lastname: Paneni
authors.forename: Thomas
authors.initials: T
authors.lastname: Lüscher
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D042783:Endothelial Cells / Q000166:cytology; D055354:Exosomes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D055018:Hemangioblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D014162:Transfection
chemical_list: D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D018950:Lipopolysaccharide Receptors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D005947:Glucose