Abstract 1168: Transient Systemic Hypoxia without Ischemic Injury Mobilizes Endothelial Progenitor Cells in Human Peripheral Blood
Background: Systemic hypoxia has been shown to increase capillary density in brain or myocardium in animal models, which suggests hypoxia-induced neovasculogenesis. However, there is no evidence that systemic hypoxia without ischemic injury mobilizes endothelial progenitor cells (EPCs). In the present study, we investigated whether systemic hypoxia recruits EPCs into human peripheral blood.
Methods and results: Twelve healthy volunteers who were undergoing an aircrew training course were subjected to hypoxic hypoxia in the hypobaric chamber under monitoring of electrocardiogram, blood pressure, oxygen saturation and mental status. Hypoxic hypoxia equal to the altitude of 15,000 feet (4,572m, estimated PaO2: 45 mmHg, measured O2 saturation was 80 ± 4%) was induced and maintained for 30 minutes. Blood samples were obtained at predetermined time points: pre-exposure and post-exposure 6hr. Levels of VEGF, IL-8, MCP-1, SDF-1, G-CSF and EPO were measured using ELISA to evaluate the level of EPC mobilizers in response to hypoxia. Number of EPCs (AC133+ or CD34+/KDR+) in the peripheral blood was quantified using flow cytometry. We performed EPC culture and compared the size and number of the EPC colonies. We found that the levels of VEGF were significantly increased 6 h after hypoxia exposure (VEGF: 257.2 ± 43.5 to 360.9 ± 59.1 pg/mL, p = 0.034). IL-8, however, decreased (32.0 ± 8.0 to 21.9 ± 7.6, p = 0.028) whereas the levels of MCP-1, SDF-1, G-CSF and EPO were not changed (p > 0.05). The number of AC133+ or KDR+/CD34+ cells increased significantly 6h after hypoxia (AC133+ cells: 0.17 ± 0.04 to 0.30 ± 0.06%, p = 0.045; KDR+/CD34+ cells: 0.078 ± 0.014 to 0.182 ± 0.041%, p = 0.015). In addition, the size and number of EPCs colonies were also increase after exposure to hypoxia (colony count: 10.7 ± 1.7 at pre-exposure to 15.8 ± 1.8 at 6 h, p = 0.003).
Conclusion: EPCs were acutely mobilized in the human peripheral blood after systemic hypoxia. The mobilization of EPCs may be a physiologic response to hypoxia which possibly contributes to hypoxia-induced neovasculogenesis for hypoxia adaptation