title: Fast reduction of peripheral blood endothelial progenitor cells in healthy humans exposed to acute systemic hypoxia.
abstract: There are hints that hypoxia exposure may affect the number of circulating endothelial progenitor cells (EPCs) in humans. To test this hypothesis, the concentration of EPCs was determined by flow cytometry in the peripheral blood of 10 young healthy adults before (0 h), at different times (0.5 h, 1 h, 2 h and 4 h) during a 4 h normobaric hypoxic breathing simulating 4100 m altitude, and in the following recovery breathing room air. Results were interpreted mainly on the basis of the changes in surface expression of CXC chemokine receptor-4 (CXCR-4, a chemokine receptor essential for EPC migration and homing) and the percentage of apoptotic cells, the plasmatic levels of markers of oxidative stress induced by hypoxic breathing. Compared to 0 h, the concentration of EPCs, identified as either CD45(dim)/CD34(+)/KDR(+) or CD45(dim)/CD34(+)/KDR(+)/CD133(+) cells, decreased from 337 ± 83 ml(-1) (mean ± SEM) to 223 ± 52 ml(-1) (0.5 h; P < 0.005) and 100 ± 37 ml(-1) (4 h; P < 0.005), and from 216 ± 91 to 161 ± 50 ml(-1) (0.5 h; P < 0.05) and 45 ± 23 ml(-1) (4 h; P < 0.005), respectively. Upon return to normoxia, their concentration increased slowly, and after 4 h was still lower than at 0 h (P < 0.05). During hypoxia, CXCR-4 expression and plasmatic stromal derived cell factor-1 (SDF-1) increased abruptly (0.5 h: +126% and +13%, respectively; P < 0.05), suggesting cell marginalization as a possible cause of the rapid hypoxia-induced EPC reduction. Moreover, hypoxia exposure induced an increase in EPC apoptosis and markers of oxidative stress, which was significantly evident only starting from 2 h and 4 h after hypoxia offset, respectively, suggesting that EPC apoptosis may contribute to the later phase of hypoxia-induced EPC reduction. Overall, these observations may provide new insights into the understanding of the mechanisms operated by EPCs to maintain endothelial homeostasis.
authors.affiliation: Department of Biomedical Sciences and Technologies, Laboratory of Immunology, University of Milan, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Colombo
authors.forename: Claudio
authors.initials: C
authors.lastname: Marconi
authors.forename: Adriano
authors.initials: A
authors.lastname: Taddeo
authors.forename: Monica
authors.initials: M
authors.lastname: Cappelletti
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Villa
authors.forename: Mauro
authors.initials: M
authors.lastname: Marzorati
authors.forename: Simone
authors.initials: S
authors.lastname: Porcelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vezzoli
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Bella
mesh_terms: D000328:Adult; D017209:Apoptosis; D002452:Cell Count; D054377:Chemokine CXCL12 / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D050050:Protein Carbonylation; D019718:Receptors, CXCR4 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D017392:Thiobarbituric Acid Reactive Substances; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A