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Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis
Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

Raynaud's phenomenon (RP) is often the first sign of systemic sclerosis (SSc). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SSc. Free thiol groups play a protective role against oxidative stress and may represent an attractive therapeutic target. We aimed to investigate the effects of hypothermia-induced vasoconstriction on the responsiveness of redox-related markers. Thirty participants (n = 10/group [SSc, primary Raynaud's phenomenon (PRP), healthy controls (HC)]) were included in this study. Fingertip photoelectric plethysmography was performed during a standardized cooling and recovery experiment. Venous blood was collected at four predetermined time points. Free thiols, NO-derived species (nitros(yl)ated species, nitrite, nitrate), sulfate and endothelin-1 were measured. Lower baseline concentrations of free thiols were observed in PRP and SSc patients (HC: 5.87 [5.41-5.99] μmol/g; PRP: 5.17 [4.74-5.61]; SSc 5.28 [4.75-5.80], P = 0.04). Redox-related markers remained unchanged during cooling. However, an unexpected increase in systemic free thiol concentrations was observed in all groups during the recovery phase. The response of this marker differed between groups, with a higher increase found in SSc patients (HC Δ = 1.30 [1.48-1.17]; PRP Δ = 1.04 [1.06-1.03]; SSc Δ = 1.72 [1.13-1.49], P = 0.04). NO-derived species, sulfate and endothelin-1 levels remained unchanged throughout the recovery phase. This exploratory study sheds light on the rapid responsiveness of systemic free thiol concentrations following reperfusion, which may reflect overall redox balance. The robust response to reperfusion in SSc patients suggests that reductive systems involved in this response are functionally intact in these patients.

e14017
Abdulle, Amaal Eman
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van Roon, Anniek M.
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Smit, Andries J.
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Pasch, Andreas
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van Meurs, Matijs
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Bootsma, Hendrika
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Bakker, Stephan J.L.
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Said, Mohammad Y.
ee2df58f-9b87-4edf-aab5-085728dd6642
Fernandez, Bernadette O.
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Feelisch, Martin
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van Goor, Harry
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Mulder, Douwe J.
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Abdulle, Amaal Eman
9b1327da-4063-445c-abcf-d2a27a932be1
van Roon, Anniek M.
8caab310-5af8-4b8b-b44c-f90aefa13281
Smit, Andries J.
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Pasch, Andreas
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van Meurs, Matijs
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Bootsma, Hendrika
68e80d3d-657b-4c7c-9690-77f3af70c0b6
Bakker, Stephan J.L.
48ec36f5-acbd-4cc3-82dd-3a8b7cb038f0
Said, Mohammad Y.
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Fernandez, Bernadette O.
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Feelisch, Martin
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van Goor, Harry
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Mulder, Douwe J.
5bc391e2-d754-431b-bef9-083c17cb5304

Abdulle, Amaal Eman, van Roon, Anniek M., Smit, Andries J., Pasch, Andreas, van Meurs, Matijs, Bootsma, Hendrika, Bakker, Stephan J.L., Said, Mohammad Y., Fernandez, Bernadette O., Feelisch, Martin, van Goor, Harry and Mulder, Douwe J. (2019) Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis. Physiological Reports, 7 (6), e14017. (doi:10.14814/phy2.14017).

Record type: Article

Abstract

Raynaud's phenomenon (RP) is often the first sign of systemic sclerosis (SSc). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SSc. Free thiol groups play a protective role against oxidative stress and may represent an attractive therapeutic target. We aimed to investigate the effects of hypothermia-induced vasoconstriction on the responsiveness of redox-related markers. Thirty participants (n = 10/group [SSc, primary Raynaud's phenomenon (PRP), healthy controls (HC)]) were included in this study. Fingertip photoelectric plethysmography was performed during a standardized cooling and recovery experiment. Venous blood was collected at four predetermined time points. Free thiols, NO-derived species (nitros(yl)ated species, nitrite, nitrate), sulfate and endothelin-1 were measured. Lower baseline concentrations of free thiols were observed in PRP and SSc patients (HC: 5.87 [5.41-5.99] μmol/g; PRP: 5.17 [4.74-5.61]; SSc 5.28 [4.75-5.80], P = 0.04). Redox-related markers remained unchanged during cooling. However, an unexpected increase in systemic free thiol concentrations was observed in all groups during the recovery phase. The response of this marker differed between groups, with a higher increase found in SSc patients (HC Δ = 1.30 [1.48-1.17]; PRP Δ = 1.04 [1.06-1.03]; SSc Δ = 1.72 [1.13-1.49], P = 0.04). NO-derived species, sulfate and endothelin-1 levels remained unchanged throughout the recovery phase. This exploratory study sheds light on the rapid responsiveness of systemic free thiol concentrations following reperfusion, which may reflect overall redox balance. The robust response to reperfusion in SSc patients suggests that reductive systems involved in this response are functionally intact in these patients.

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Accepted/In Press date: 28 January 2019
e-pub ahead of print date: 27 March 2019
Published date: March 2019
Additional Information: © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Identifiers

Local EPrints ID: 430263
URI: https://eprints.soton.ac.uk/id/eprint/430263
PURE UUID: a7d86b25-3140-492c-a1b0-1a6a8ef4bd5f
ORCID for Bernadette O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 23 Apr 2019 16:30
Last modified: 25 Apr 2019 00:31

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Contributors

Author: Amaal Eman Abdulle
Author: Anniek M. van Roon
Author: Andries J. Smit
Author: Andreas Pasch
Author: Matijs van Meurs
Author: Hendrika Bootsma
Author: Stephan J.L. Bakker
Author: Mohammad Y. Said
Author: Bernadette O. Fernandez ORCID iD
Author: Martin Feelisch ORCID iD
Author: Harry van Goor
Author: Douwe J. Mulder

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