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FRI0426 Response of the reactive species interactome to hypothermia induced raynaud’s attack in primary raynaud and systemic sclerosis

FRI0426 Response of the reactive species interactome to hypothermia induced raynaud’s attack in primary raynaud and systemic sclerosis
FRI0426 Response of the reactive species interactome to hypothermia induced raynaud’s attack in primary raynaud and systemic sclerosis
Background: Although the exact etiology of systemic sclerosis (SSc) remains unknown, a current hypothesis is that reactive species (including reactive oxygen species (ROS), reactive nitrogen species (RNS and reactive sulfur species (RSS)) play an important role in the pathogenesis. In addition, the chemical interactions between these molecules, also known as the reactive species interactome, may lead to the formation of more harmful free radicals, thus leading to more damage. We have previously shown a rapid free thiol increase in SSc patients during a cooling and recovery experiment, however the implications of RNS and RSS in this process remain uncharacterized. Objectives: The aim of the current study was to explore nitric oxide and sulfate response, as a measure of the unified reactive species interactome, during hypothermia induced Raynaud’s attack in systemic sclerosis (SSc), primary Raynaud’s phenomenon (PRP) and healthy controls (HC). Methods: Healthy controls (n=10), PRP patients (n=10) and SSc patients (n=10), all aged ≥18 years, were included. All SSc patients fulfilled the ACR/EULAR 2013 criteria. Fingertip photoelectric plethysmography was performed during a standardised cooling and recovery experiment. Patient characteristics were obtained and blood was drawn at four predetermined time points (T0, T1, T2 and T3). In addition to the previously mentioned free thiols, the following markers were also measured: nitros(yl)ated species, nitrite, nitrate, sulfate and the vascular leakage related molecules angiopoietin-1 and angiopoietin-2). Results: Our results revealed a significantly longer median duration of hypoperfusion and longer recovery time in SSc patients compared to PRP patients and HC. This coincided with stable levels of angiopoietin-1/angiopoietin-2 throughout the experiment. In regards to the thiol modification related molecules, (nitrate, nitrite and RXNO) an increased median level of nitrate (T2: median 29.6 µmol, range 21.99–41.70 µmol, p=0.041) was found in SSc patients. Correspondingly, the same trend was observed for the median plasma concentrations of sulfate (p>0.05 at all time points).
0003-4967
743-744
Abdulle, A. Eman
9b1327da-4063-445c-abcf-d2a27a932be1
van Roon, A.M.
8caab310-5af8-4b8b-b44c-f90aefa13281
Smit, A.J.
dacc2abc-a1fa-4851-a095-40248251fc61
Pasch, A.
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van Meurs, M.
8042c1e4-8fb2-407f-a3ac-47a8a18b44b8
Bootsma, H.
68e80d3d-657b-4c7c-9690-77f3af70c0b6
Fernandez, B.O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, M.
8c1b9965-8614-4e85-b2c6-458a2e17eafd
van Goor, H.
fadc9a49-233e-40c3-9e05-8713ffbc02e5
Mulder, D.J.
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Abdulle, A. Eman
9b1327da-4063-445c-abcf-d2a27a932be1
van Roon, A.M.
8caab310-5af8-4b8b-b44c-f90aefa13281
Smit, A.J.
dacc2abc-a1fa-4851-a095-40248251fc61
Pasch, A.
5f5d9b34-4d9e-40a4-9326-fa1cd352717d
van Meurs, M.
8042c1e4-8fb2-407f-a3ac-47a8a18b44b8
Bootsma, H.
68e80d3d-657b-4c7c-9690-77f3af70c0b6
Fernandez, B.O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, M.
8c1b9965-8614-4e85-b2c6-458a2e17eafd
van Goor, H.
fadc9a49-233e-40c3-9e05-8713ffbc02e5
Mulder, D.J.
5bc391e2-d754-431b-bef9-083c17cb5304

Abdulle, A. Eman, van Roon, A.M., Smit, A.J., Pasch, A., van Meurs, M., Bootsma, H., Fernandez, B.O., Feelisch, M., van Goor, H. and Mulder, D.J. (2018) FRI0426 Response of the reactive species interactome to hypothermia induced raynaud’s attack in primary raynaud and systemic sclerosis. Annals of the Rheumatic Diseases, 77 (2), 743-744. (doi:10.1136/annrheumdis-2018-eular.7051).

Record type: Article

Abstract

Background: Although the exact etiology of systemic sclerosis (SSc) remains unknown, a current hypothesis is that reactive species (including reactive oxygen species (ROS), reactive nitrogen species (RNS and reactive sulfur species (RSS)) play an important role in the pathogenesis. In addition, the chemical interactions between these molecules, also known as the reactive species interactome, may lead to the formation of more harmful free radicals, thus leading to more damage. We have previously shown a rapid free thiol increase in SSc patients during a cooling and recovery experiment, however the implications of RNS and RSS in this process remain uncharacterized. Objectives: The aim of the current study was to explore nitric oxide and sulfate response, as a measure of the unified reactive species interactome, during hypothermia induced Raynaud’s attack in systemic sclerosis (SSc), primary Raynaud’s phenomenon (PRP) and healthy controls (HC). Methods: Healthy controls (n=10), PRP patients (n=10) and SSc patients (n=10), all aged ≥18 years, were included. All SSc patients fulfilled the ACR/EULAR 2013 criteria. Fingertip photoelectric plethysmography was performed during a standardised cooling and recovery experiment. Patient characteristics were obtained and blood was drawn at four predetermined time points (T0, T1, T2 and T3). In addition to the previously mentioned free thiols, the following markers were also measured: nitros(yl)ated species, nitrite, nitrate, sulfate and the vascular leakage related molecules angiopoietin-1 and angiopoietin-2). Results: Our results revealed a significantly longer median duration of hypoperfusion and longer recovery time in SSc patients compared to PRP patients and HC. This coincided with stable levels of angiopoietin-1/angiopoietin-2 throughout the experiment. In regards to the thiol modification related molecules, (nitrate, nitrite and RXNO) an increased median level of nitrate (T2: median 29.6 µmol, range 21.99–41.70 µmol, p=0.041) was found in SSc patients. Correspondingly, the same trend was observed for the median plasma concentrations of sulfate (p>0.05 at all time points).

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More information

e-pub ahead of print date: 12 June 2018
Published date: 12 June 2018
Additional Information: Congress of the European-League-Against-Rheumatism (EULAR), Amsterdam, NETHERLANDS, JUN 13-16, 2018

Identifiers

Local EPrints ID: 447312
URI: http://eprints.soton.ac.uk/id/eprint/447312
ISSN: 0003-4967
PURE UUID: adad0a23-7dc8-46a6-a7eb-6948756d7900
ORCID for B.O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for M. Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 09 Mar 2021 17:31
Last modified: 10 Mar 2021 02:43

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Contributors

Author: A. Eman Abdulle
Author: A.M. van Roon
Author: A.J. Smit
Author: A. Pasch
Author: M. van Meurs
Author: H. Bootsma
Author: B.O. Fernandez ORCID iD
Author: M. Feelisch ORCID iD
Author: H. van Goor
Author: D.J. Mulder

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