title: Type 2 diabetes mellitus impairs the maturation of endothelial progenitor cells and increases the number of circulating endothelial cells in peripheral blood.
abstract: Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, which leads to vascular complications. Endothelial progenitor cells (EPCs) are thought to be a subset of cells derived from the bone marrow that play a crucial role in the neovascularization of ischemic tissue and in the maintenance of endothelial cell integrity. In contrast, circulating endothelial cells (CECs) are of endothelial origin and become detached from the intima of blood vessels in response to pathological stimuli. The study investigated the effects of T2DM on subpopulations of EPCs and CECs in peripheral blood, as compared with the effects on unacylated (UAG) and acylated (AG) ghrelin levels, which have been shown recently to play an important role in endothelial dysfunction associated with diabetes. Using the high-performance flow cytometer FACSCanto, and UAG/AG ghrelin enzyme immunoassay kits, we analyzed whole peripheral blood samples from: (i) diabetic patients with a history of disease of less than 1 year and no clinical evidence of angiopathy, (ii) diabetic patients with long-standing disease with vascular complications, and (iii) healthy donors. We found that T2DM did not affect bone-marrow mobilization, but it altered the UAG/AG profile and decreased the number of highly differentiated EPCs (late EPCs) greatly. In addition, T2DM increased the number of CECs, together with the number of activated CECs. Our results suggest that: (i) the endothelial damage could be due mainly to altered maturation/commitment of EPCs, rather than a simple decrease in their production in the bone marrow; and (ii) EPC subpopulations and ghrelin levels could be useful markers to assess endothelial damage in diabetes.
authors.affiliation: Centro Unico Regionale Trapianti Midollo Osseo e Terapie Cellulari Alberto Neri, Azienda Ospedaliera Bianchi-Melacrino-Morelli, 89100 Reggio Calabria, Italy.
authors.forename: Marco F
authors.initials: MF
authors.lastname: Lombardo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Iacopino
authors.forename: Maria
authors.initials: M
authors.lastname: Cuzzola
authors.forename: Elisa
authors.initials: E
authors.lastname: Spiniello
authors.forename: Cristina
authors.initials: C
authors.lastname: Garreffa
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppola
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Alberto
authors.initials: A
authors.lastname: Piaggesi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Piro
authors.forename: Domenico
authors.initials: D
authors.lastname: Mannino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grossi
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Irrera
mesh_terms: D000215:Acylation; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000276:immunology / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D054439:Ghrelin / Q000097:blood; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000097:blood; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*
chemical_list: D015415:Biomarkers; D054439:Ghrelin; D020033:Protein Isoforms