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Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?

Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?
Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this ‘Reactive Species Interactome’ (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable ‘metabolic signatures’ to a defined physiological challenge could potentially offer new avenues for personalised medicine.
Altitude, Hydrogen sulfide, Hypoxia, Oxidative stress, Oxygen, Thiols
2213-2317
1-12
Cumpstey, Andrew F.
225ec09e-0312-4c7a-8049-c6e5acd87436
Minnion, Magdalena
ab23b32b-9f8e-4876-aaf5-99cb6a725a2f
Fernandez, Bernadette
9890aabc-1fe6-4530-a51e-31182e537131
Mikus-Lelinska, Monika
6ca48669-ff8f-4ae8-9d10-98c74327b4ec
Mitchell, Kay
f57f07cd-0e3a-48b2-a871-c436eec325ae
Martin, Dan S.
50243932-6bc7-4780-ae4c-599ebcb04fee
Grocott, Michael
1e87b741-513e-4a22-be13-0f7bb344e8c2
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Cumpstey, Andrew F.
225ec09e-0312-4c7a-8049-c6e5acd87436
Minnion, Magdalena
ab23b32b-9f8e-4876-aaf5-99cb6a725a2f
Fernandez, Bernadette
9890aabc-1fe6-4530-a51e-31182e537131
Mikus-Lelinska, Monika
6ca48669-ff8f-4ae8-9d10-98c74327b4ec
Mitchell, Kay
f57f07cd-0e3a-48b2-a871-c436eec325ae
Martin, Dan S.
50243932-6bc7-4780-ae4c-599ebcb04fee
Grocott, Michael
1e87b741-513e-4a22-be13-0f7bb344e8c2
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd

Cumpstey, Andrew F., Minnion, Magdalena, Fernandez, Bernadette, Mikus-Lelinska, Monika, Mitchell, Kay, Martin, Dan S., Grocott, Michael and Feelisch, Martin (2019) Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics? Redox Biology, 21, 1-12. (doi:10.1016/j.redox.2019.101113).

Record type: Article

Abstract

The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this ‘Reactive Species Interactome’ (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable ‘metabolic signatures’ to a defined physiological challenge could potentially offer new avenues for personalised medicine.

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Accepted/In Press date: 14 January 2019
e-pub ahead of print date: 22 January 2019
Published date: 6 February 2019
Keywords: Altitude, Hydrogen sulfide, Hypoxia, Oxidative stress, Oxygen, Thiols

Identifiers

Local EPrints ID: 428244
URI: https://eprints.soton.ac.uk/id/eprint/428244
ISSN: 2213-2317
PURE UUID: e5185b67-707a-4731-85e3-bdb2d04e445e
ORCID for Bernadette Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Kay Mitchell: ORCID iD orcid.org/0000-0001-6393-8475
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 18 Feb 2019 17:30
Last modified: 20 Jul 2019 00:43

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Contributors

Author: Andrew F. Cumpstey
Author: Magdalena Minnion
Author: Bernadette Fernandez ORCID iD
Author: Monika Mikus-Lelinska
Author: Kay Mitchell ORCID iD
Author: Dan S. Martin
Author: Michael Grocott
Author: Martin Feelisch ORCID iD

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