Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema

Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen ac...

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Main Authors: Matthias Peter Hilty, Stefanie Zügel, Michele Schoeb, Katja Auinger, Christoph Dehnert, Marco Maggiorini
Format: Article
Language:English
Published: Hindawi Limited 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/1942460
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author Matthias Peter Hilty
Stefanie Zügel
Michele Schoeb
Katja Auinger
Christoph Dehnert
Marco Maggiorini
author_facet Matthias Peter Hilty
Stefanie Zügel
Michele Schoeb
Katja Auinger
Christoph Dehnert
Marco Maggiorini
author_sort Matthias Peter Hilty
collection DOAJ
description Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9±0.4 at SL versus 2.3±0.5 at HA, p<0.01), CRP (0.7±0.5 at SL versus 3.6±4.6 at HA, p<0.01), and IL-6 (0.8±0.4 at SL versus 3.3±4.9 at HA, p<0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r=0.46, p<0.001), but not suPAR (r=0.27, p=0.08); the increase in IL-6 was not correlated with suPAR (r=0.16, p=0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0±0.4 versus 1.8±0.4, p=0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict HAPE susceptibility.
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spelling doaj.art-d0e864fb24994890b1bcafcacb71eabc2022-12-22T03:56:55ZengHindawi LimitedMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/19424601942460Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary EdemaMatthias Peter Hilty0Stefanie Zügel1Michele Schoeb2Katja Auinger3Christoph Dehnert4Marco Maggiorini5Medical Intensive Care Unit, University Hospital of Zurich, 8091 Zurich, SwitzerlandInstitute for Sports Medicine, Ruprecht-Karls University of Heidelberg, 69117 Heidelberg, GermanyMedical Intensive Care Unit, University Hospital of Zurich, 8091 Zurich, SwitzerlandMedical Intensive Care Unit, University Hospital of Zurich, 8091 Zurich, SwitzerlandInstitute for Sports Medicine, Ruprecht-Karls University of Heidelberg, 69117 Heidelberg, GermanyMedical Intensive Care Unit, University Hospital of Zurich, 8091 Zurich, SwitzerlandIntroduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9±0.4 at SL versus 2.3±0.5 at HA, p<0.01), CRP (0.7±0.5 at SL versus 3.6±4.6 at HA, p<0.01), and IL-6 (0.8±0.4 at SL versus 3.3±4.9 at HA, p<0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r=0.46, p<0.001), but not suPAR (r=0.27, p=0.08); the increase in IL-6 was not correlated with suPAR (r=0.16, p=0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0±0.4 versus 1.8±0.4, p=0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict HAPE susceptibility.http://dx.doi.org/10.1155/2016/1942460
spellingShingle Matthias Peter Hilty
Stefanie Zügel
Michele Schoeb
Katja Auinger
Christoph Dehnert
Marco Maggiorini
Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
Mediators of Inflammation
title Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
title_full Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
title_fullStr Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
title_full_unstemmed Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
title_short Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema
title_sort soluble urokinase type plasminogen activator receptor plasma concentration may predict susceptibility to high altitude pulmonary edema
url http://dx.doi.org/10.1155/2016/1942460
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