Fast reduction of peripheral blood endothelial progenitor cells in healthy humans exposed to acute systemic hypoxia

Elena Colombo, Claudio Marconi, Adriano Taddeo, Monica Cappelletti, Maria Luisa Villa, Mauro Marzorati, Simone Porcelli, Alessandra Vezzoli, Silvia Della Bella

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)519-532
Number of pages14
JournalJournal of Physiology
Volume590
Issue number3
DOIs
Publication statusPublished - Feb 2012

ASJC Scopus subject areas

  • Physiology

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