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

• Published in: PloS one 2021-07, Vol.16 (7), p.e0253247-e0253247
• Main Authors: Deyab, Gia, Reine, Trine Marita, Vuong, Tram Thu, Jenssen, Trond, Hjeltnes, Gunnbjørg, Agewall, Stefan, Mikkelsen, Knut, Førre, Øystein, Fagerland, Morten Wang, Kolset, Svein Olav, Hollan, Ivana
• Format: Article
• Language: English
• Subjects: Antirheumatic agents; Arthritis; Atherogenesis; Atherosclerosis; Biology and Life Sciences; Cardiovascular diseases; Chemokines; Chronic illnesses; Disease; Dosage and administration; Drug therapy; Endothelial cells; Endothelium; Gelatinase B; Health aspects; Health risks; Health sciences; Hospitals; Inflammation; Laboratories; Matrix metalloproteinase; Matrix metalloproteinases; Measurement; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Membrane proteins; Metabolism; Metalloproteinase; Methotrexate; Mortality; Nephrology; Pathogenesis; Patients; Physical Sciences; Physiological aspects; R&D; Research & development; Research and Analysis Methods; Rheumatoid arthritis; Rheumatology; Serum levels; Shedding; Statistical analysis; Syndecan; Tissue inhibitor of metalloproteinase 1; TNF inhibitors; Tumor necrosis factor-TNF; Vascular diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0253247

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