PMID- 35887981 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230308 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 11 IP - 14 DP - 2022 Jul 20 TI - TNF-alpha Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis. LID - 10.3390/jcm11144213 [doi] LID - 4213 AB - Sulfated glycosaminoglycans (sGAGs) are likely to play an important role in the development and progression of rheumatoid arthritis (RA)-associated atherosclerosis. The present study investigated the effect of anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy in combination with methotrexate on plasma sGAG levels and serum markers of endothelial dysfunction. Among sGAG types, plasma chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) were characterized using electrophoretic fractionation. Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and asymmetric dimethylarginine (ADMA) were measured by immunoassays. The measurements were carried out four times: at baseline and after 3, 9 and 15 months of anti-TNF-alpha therapy. All analyzed parameters, excluding ADMA, were significantly elevated in patients with RA before the implementation of biological therapy compared to healthy subjects. Performed anti-TNF-alpha treatment led to a successive decrease in HS/H levels toward normal values, without any effect on CS/DS levels in female RA patients. The treatment was also effective at lowering the serum levels of sVCAM-1, MCP-1, MMP-9 and ADMA. Moreover, a significant positive correlation was found between the circulating HS/H and the 28 joint disease activity score based on the erythrocyte sedimentation rate (DAS28-ESR, r = 0.408; p <0.05), MCP-1 (r = 0.398; p <0.05) and ADMA (r = 0.396; p <0.05) in patients before the first dose of TNF-alpha inhibitor. In conclusion, a beneficial effect of anti-TNF-alpha therapy on cell-surface heparan sulfate proteoglycans (HSPGs)/HS turnover and endothelial dysfunction was observed in this study. This was manifested by a decrease in blood HS/H levels and markers of endothelial activation, respectively. Moreover, the decrease in the concentration of HS/H in the blood of patients during treatment, progressing with the decline in disease activity, indicates that the plasma HS/H profile may be useful for monitoring the efficacy of anti-TNF-alpha treatment in patients with RA. FAU - Szeremeta, Anna AU - Szeremeta A AUID- ORCID: 0000-0001-8445-2490 AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 8, 41-200 Sosnowiec, Poland. FAU - Jura-Poltorak, Agnieszka AU - Jura-Poltorak A AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 8, 41-200 Sosnowiec, Poland. FAU - Zon-Giebel, Aleksandra AU - Zon-Giebel A AD - Department of Rheumatology and Rehabilitation, Specialty Hospital No. 1, Zeromskiego 7, 41-902 Bytom, Poland. FAU - Olczyk, Krystyna AU - Olczyk K AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 8, 41-200 Sosnowiec, Poland. FAU - Komosinska-Vassev, Katarzyna AU - Komosinska-Vassev K AUID- ORCID: 0000-0003-2307-5884 AD - Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 8, 41-200 Sosnowiec, Poland. LA - eng GR - PCN-2-064/K/1/I/Medical University of Silesia/ GR - 2013/09/N/NZ5/00815/The National Science Centre, Poland/ PT - Journal Article DEP - 20220720 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC9320287 OTO - NOTNLM OT - ADMA OT - MCP-1 OT - MMP-9 OT - anti-TNF-alpha treatment OT - heparan sulfate/heparin OT - rheumatoid arthritis OT - sVCAM-1 COIS- The authors declare no conflict of interest. EDAT- 2022/07/28 06:00 MHDA- 2022/07/28 06:01 PMCR- 2022/07/20 CRDT- 2022/07/27 01:27 PHST- 2022/06/06 00:00 [received] PHST- 2022/07/13 00:00 [revised] PHST- 2022/07/19 00:00 [accepted] PHST- 2022/07/27 01:27 [entrez] PHST- 2022/07/28 06:00 [pubmed] PHST- 2022/07/28 06:01 [medline] PHST- 2022/07/20 00:00 [pmc-release] AID - jcm11144213 [pii] AID - jcm-11-04213 [pii] AID - 10.3390/jcm11144213 [doi] PST - epublish SO - J Clin Med. 2022 Jul 20;11(14):4213. doi: 10.3390/jcm11144213.