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The role of oxidative stress in the development of systemic sclerosis related vasculopathy

The role of oxidative stress in the development of systemic sclerosis related vasculopathy
The role of oxidative stress in the development of systemic sclerosis related vasculopathy

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as 'Raynaud's phenomenon,' which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.

Biomarker, Development, Intervention, Reactive oxygen species, Systemic sclerosis, Vasculopathy
1664-042X
1-15
Abdulle, Amaal E.
b3c13bb5-fbd1-41ae-94ca-efd1a2123dda
Diercks, Gilles F.H.
54e32392-ced7-4c16-8a94-8da2c8c649e7
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Mulder, Douwe J.
5bc391e2-d754-431b-bef9-083c17cb5304
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
Abdulle, Amaal E.
b3c13bb5-fbd1-41ae-94ca-efd1a2123dda
Diercks, Gilles F.H.
54e32392-ced7-4c16-8a94-8da2c8c649e7
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Mulder, Douwe J.
5bc391e2-d754-431b-bef9-083c17cb5304
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3

Abdulle, Amaal E., Diercks, Gilles F.H., Feelisch, Martin, Mulder, Douwe J. and van Goor, Harry (2018) The role of oxidative stress in the development of systemic sclerosis related vasculopathy. Frontiers in Physiology, 9 (AUG), 1-15. (doi:10.3389/fphys.2018.01177).

Record type: Review

Abstract

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as 'Raynaud's phenomenon,' which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.

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Accepted/In Press date: 6 August 2018
e-pub ahead of print date: 24 August 2018
Published date: August 2018
Keywords: Biomarker, Development, Intervention, Reactive oxygen species, Systemic sclerosis, Vasculopathy

Identifiers

Local EPrints ID: 424390
URI: https://eprints.soton.ac.uk/id/eprint/424390
ISSN: 1664-042X
PURE UUID: 0be71218-c25d-4caa-9358-c168309bfdce
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 05 Oct 2018 11:36
Last modified: 14 Mar 2019 01:36

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Contributors

Author: Amaal E. Abdulle
Author: Gilles F.H. Diercks
Author: Martin Feelisch ORCID iD
Author: Douwe J. Mulder
Author: Harry van Goor

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