Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteris...

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Autores principales:	Gia Deyab, Trine Marita Reine, Tram Thu Vuong, Trond Jenssen, Gunnbjørg Hjeltnes, Stefan Agewall, Knut Mikkelsen, Øystein Førre, Morten Wang Fagerland, Svein Olav Kolset, Ivana Hollan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f73757932ab476da0063beea41a4747
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spelling	oai:doaj.org-article:4f73757932ab476da0063beea41a47472021-12-02T20:05:07ZAntirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.1932-620310.1371/journal.pone.0253247https://doaj.org/article/4f73757932ab476da0063beea41a47472021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253247https://doaj.org/toc/1932-6203The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.Gia DeyabTrine Marita ReineTram Thu VuongTrond JenssenGunnbjørg HjeltnesStefan AgewallKnut MikkelsenØystein FørreMorten Wang FagerlandSvein Olav KolsetIvana HollanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253247 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gia Deyab Trine Marita Reine Tram Thu Vuong Trond Jenssen Gunnbjørg Hjeltnes Stefan Agewall Knut Mikkelsen Øystein Førre Morten Wang Fagerland Svein Olav Kolset Ivana Hollan Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.
description	The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.
format	article
author	Gia Deyab Trine Marita Reine Tram Thu Vuong Trond Jenssen Gunnbjørg Hjeltnes Stefan Agewall Knut Mikkelsen Øystein Førre Morten Wang Fagerland Svein Olav Kolset Ivana Hollan
author_facet	Gia Deyab Trine Marita Reine Tram Thu Vuong Trond Jenssen Gunnbjørg Hjeltnes Stefan Agewall Knut Mikkelsen Øystein Førre Morten Wang Fagerland Svein Olav Kolset Ivana Hollan
author_sort	Gia Deyab
title	Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.
title_short	Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.
title_full	Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.
title_fullStr	Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.
title_full_unstemmed	Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.
title_sort	antirheumatic treatment is associated with reduced serum syndecan-1 in rheumatoid arthritis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4f73757932ab476da0063beea41a4747
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Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

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