Abstract
Purpose
Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed.
Methods
29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol.
Results
15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group.
Conclusion
Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.
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Abbreviations
- AMS:
-
Acute mountain sickness
- ANOVA:
-
Analysis of variance
- BH4:
-
Tetrahydrobiopterin
- CD31+MP:
-
Cluster of differentiation 31 positive microparticle also known as platelet endothelial cell adhesion molecule positive microparticle
- CD62+MP:
-
Cluster of differentiation 62 positive microparticle also known as endothelial-selectin positive microparticle
- CD144+MP:
-
Cluster of differentiation 144 positive microparticle also known as vascular endothelial-cadherin positive microparticle
- HACE:
-
High altitude cerebral edema
- HAPE:
-
High altitude pulmonary edema
- HODE:
-
Hydroxyoctadecadienoic acid
- iPF2α-III:
-
8-Iso-prostaglandin F2α
- LLS:
-
Lake Louise acute mountain sickness score
- MP:
-
Microparticles
- NAC:
-
N-acetylcysteine
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- PS:
-
Phosphatidylserine
- PS+MP:
-
Phosphatidylserine positive microparticle
- ROS:
-
Reactive oxygen species
- SpO2 :
-
Pulse oxymetric arterial oxygen saturation
- 9-HODE:
-
(±)9-Hydroxy-10E,12Z-octadecadienoic acid
- 13-HODE:
-
13(S)-Hydroxy-9Z,11E-octadecadienoic acid
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Acknowledgments
We thank all the volunteers, mountain guides, and local staff for their invaluable support of this research project. Equipment was kindly provided by Hettich AG, Bäch, Switzerland. This study was supported by the Swiss Society of Mountain Medicine.
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Communicated by Fabio Fischetti.
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Pichler Hefti, J., Leichtle, A., Stutz, M. et al. Increased endothelial microparticles and oxidative stress at extreme altitude. Eur J Appl Physiol 116, 739–748 (2016). https://doi.org/10.1007/s00421-015-3309-3
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DOI: https://doi.org/10.1007/s00421-015-3309-3