Jacqueline Pichler Hefti1,2, Alexander Leichtle3, Monika Stutz4, Urs Hefti5, Thomas Geiser6, Andreas R Huber7, Tobias M Merz8. 1. Department of Pneumology, University Hospital and University of Bern, Bern, Switzerland. Jacqueline.Pichler@Insel.ch. 2. Department of Intensive Care Medicine, University Hospital and University of Bern, Bern, Switzerland. Jacqueline.Pichler@Insel.ch. 3. University Institute of Clinical Chemistry, University Hospital and University of Bern, Bern, Switzerland. 4. Department of Clinical Investigation, University Hospital and University of Bern, Bern, Switzerland. 5. Swiss Sportsclinic, Bern, Switzerland. 6. Department of Pneumology, University Hospital and University of Bern, Bern, Switzerland. 7. Center of Laboratory Medicine, Cantonal Hospital Aarau, Aarau, Switzerland. 8. Department of Intensive Care Medicine, University Hospital and University of Bern, Bern, Switzerland.
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.
RCT Entities:
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.
Authors: Marc M Berger; Christiane Hesse; Christoph Dehnert; Heike Siedler; Petra Kleinbongard; Hubert J Bardenheuer; Malte Kelm; Peter Bärtsch; Walter E Haefeli Journal: Am J Respir Crit Care Med Date: 2005-06-09 Impact factor: 21.405
Authors: Nia C S Lewis; Damian M Bailey; Gregory R Dumanoir; Laura Messinger; Samuel J E Lucas; James D Cotter; Joseph Donnelly; Jane McEneny; Ian S Young; Mike Stembridge; Keith R Burgess; Aparna S Basnet; Philip N Ainslie Journal: J Physiol Date: 2013-12-09 Impact factor: 5.182
Authors: Todd M Bull; Heiko Golpon; Robert P Hebbel; Anna Solovey; Carlyne D Cool; Rubin M Tuder; Mark W Geraci; Norbert F Voelkel Journal: Thromb Haemost Date: 2003-10 Impact factor: 5.249