Circulating Endothelial Cell Number and Viability Are Reduced by Exposure to High Altitude

Mancuso, Patrizia; Peccatori, Fedro Alessandro; Rocca, Andrea; Calleri, Angelica; Antoniotti, Pierluigi; Rabascio, Cristina; Saronni, Luca; Zorzino, Laura; Sandri, Maria Teresa; Zubani, Anna

doi:10.1080/10623320802092344

Cited by 12 publications

(15 citation statements)

References 26 publications

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“…To our knowledge, so far few studies have addressed the effects of acute or subacute exposure to hypoxia on EPC homeostasis, yet reporting controversial results. In fact either a reduction (Mancuso et al 2008) or an increase (Theiss et al 2008) in EPCs was found after a 7–12 day sojourn at altitudes ranging from 1700 to 5000 m. By contrast, a 3 h intermittent hypobaric hypoxia exposure equivalent to 5000 m altitude for three consecutive days failed to change EPC concentration in four subjects (Viscor et al 2009), whereas a 1 h bout of normobaric hypoxia equivalent to 4850 m increased EPCs by approximately 70% (Ciulla et al 2007). These conflicting results may depend on a variety of factors, including degree and mode of hypoxia exposure, number and homogeneity of investigated subjects, concomitant physical activity, timing of blood sampling, time‐span before analysis, analytical procedures and inter‐individual variability of the measure.…”

Section: Discussionmentioning

confidence: 97%

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

Colombo

Marconi

Taddeo

et al. 2012

The Journal of Physiology

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Non-technical summary The endothelium is a thin layer of cells lining the interior surface of the entire circulatory system. Endothelial progenitor cells (EPCs) have a crucial role in maintaining the integrity of the endothelium, as they are recruited from the bone marrow to sites of endothelial injury where they contribute to blood vessel formation and repair. The factors regulating EPC mobilization and trafficking remain incompletely understood. We evaluated the time-course effects of a single 4 h bout of severe hypoxic breathing (simulating 4100 m altitude) followed by 4 h restoration in room air. We show that hypoxia alone induces a rapid disappearance of EPCs from blood, probably sustained by a prompt cell marginalization followed by a late increase in EPC apoptosis. These observations may broaden our understanding of the mechanisms operated by EPCs to maintain endothelial homeostasis and may help to elucidate the potential role of EPCs in regenerative medicine.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.

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Section: Discussionmentioning

confidence: 97%

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

Colombo

Marconi

Taddeo

et al. 2012

The Journal of Physiology

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“…Specifically, hypoxia decreased CPC count in two normobaric hypoxia studies involving a total of 20 subjects [32,33], and also in a hypobaric hypoxia study with 15 mountain trekkers [34]. Different types and intensities of physical exercise have also been shown to be capable of mobilizing CPC.…”

Section: Discussionmentioning

confidence: 99%

Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

Corral

Javierre

Blasi

et al. 2014

Journal of Translational Medicine

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BackgroundOur goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC) and increase their concentration in peripheral circulation.MethodsNine healthy male subjects were subjected, as the active group (HME), to a protocol involving IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric pressure of 540 hPa (equivalent to an altitude of 5000 m). These sessions took place on four consecutive days. ME was applied in two separate 20-minute periods during each IHH session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment, and then 24 h, 48 h, 4 days, 7 days and 14 days after the last day of hypoxic exposure. Four months later a control study was carried out involving seven of the original subjects (CG), who underwent the same protocol of blood samples but without receiving any special stimulus.ResultsIn comparison with the CG the HME group showed only a non-significant increase in the number of CPC CD34+ cells on the fourth day after the combined IHH and ME treatment.ConclusionCPC levels oscillated across the study period and provide no firm evidence to support an increased CPC count after IHH plus ME, although it is not possible to know if this slight increase observed is physiologically relevant. Further studies are required to understand CPC dynamics and the physiology and physiopathology of the hypoxic stimulus.

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“…[7] A study on the effect of exposure to high altitude showed that these endothelial populations were reduced after high altitude exposure for 12 days in 15 mountain trekkers. [8] On the other hand, both CECs and CPCs are reportedly unchanged in obstructive sleep apnea without manifestations of PAH. [9] Furthermore, in the study on EPCs in SSc-PAH, [7] it was suggested that there is an increase in EPCs in the initial stage of PAH, when EPCs contribute to pathologic vascular remodeling.…”

Section: Commentarymentioning

confidence: 98%

Commentary - Distinct patterns of circulating endothelial cells in pulmonary hypertension

Menon¹

2010

PVRI Review

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Circulating Endothelial Cell Number and Viability Are Reduced by Exposure to High Altitude

Cited by 12 publications

References 26 publications

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

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

Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

Commentary - Distinct patterns of circulating endothelial cells in pulmonary hypertension

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