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The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis
OBJECTIVES: Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undef...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213430/ https://www.ncbi.nlm.nih.gov/pubmed/33313793 http://dx.doi.org/10.1093/rheumatology/keaa725 |
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author | Davies, Ruth Williams, Jessica Sime, Katie Jin, Hyun-Sun Thompson, Charlotte Jordan, Lauren Lang, Derek Halcox, Julian P Ellins, Elizabeth Jones, Gareth W Jones, Simon A Rose-John, Stefan Williams, Anwen Choy, Ernest |
author_facet | Davies, Ruth Williams, Jessica Sime, Katie Jin, Hyun-Sun Thompson, Charlotte Jordan, Lauren Lang, Derek Halcox, Julian P Ellins, Elizabeth Jones, Gareth W Jones, Simon A Rose-John, Stefan Williams, Anwen Choy, Ernest |
author_sort | Davies, Ruth |
collection | PubMed |
description | OBJECTIVES: Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA. METHODS: Myography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT). RESULTS: sgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT ‘rapid progressors’ at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol. CONCLUSIONS: IL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population. |
format | Online Article Text |
id | pubmed-8213430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82134302021-06-21 The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis Davies, Ruth Williams, Jessica Sime, Katie Jin, Hyun-Sun Thompson, Charlotte Jordan, Lauren Lang, Derek Halcox, Julian P Ellins, Elizabeth Jones, Gareth W Jones, Simon A Rose-John, Stefan Williams, Anwen Choy, Ernest Rheumatology (Oxford) Clinical Science OBJECTIVES: Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA. METHODS: Myography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT). RESULTS: sgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT ‘rapid progressors’ at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol. CONCLUSIONS: IL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population. Oxford University Press 2020-12-11 /pmc/articles/PMC8213430/ /pubmed/33313793 http://dx.doi.org/10.1093/rheumatology/keaa725 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Science Davies, Ruth Williams, Jessica Sime, Katie Jin, Hyun-Sun Thompson, Charlotte Jordan, Lauren Lang, Derek Halcox, Julian P Ellins, Elizabeth Jones, Gareth W Jones, Simon A Rose-John, Stefan Williams, Anwen Choy, Ernest The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
title | The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
title_full | The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
title_fullStr | The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
title_full_unstemmed | The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
title_short | The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
title_sort | role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis |
topic | Clinical Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213430/ https://www.ncbi.nlm.nih.gov/pubmed/33313793 http://dx.doi.org/10.1093/rheumatology/keaa725 |
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