Background/Purpose: Glycosylation has been reported to associate with tumor invasion and metastasis. Fucosylation is involved the biological functions of adhesion molecules and growth factor receptors. In regards to arthritis, we have previously reported that fucosylated proteins were expressed on rheumatoid arthritis (RA) synovial tissues. Here, we examined the expression of fucosylated proteins in RA and mediates angiogenesis.

Methods: Total glycans were determined in serum from normal (NL) subjects and RA patients using mass spectrometry. To determine whether fcosylated proteins involved with RA inflammation, the correlation with disease activity score (DAS) 28 (ESR) was measured. 2-deoxy-D-galactose (2-dGal) is an analog of hexose that inhibits fucosylation. In order to confirm the role of fucosylation in RA angiogenesis, we did Matrigel assays in vitro. To block the expression of fcosylated proteins, human umbilical vein endothelial cells (HUVECs) were treated with 2-dGal (15 mM) for 5 days. After treatment with 2-dGal, HUVECs were plated on Matrigel and were incubated with phosphate buffered saline (PBS) or RA synovial fluids. Finally, expression of proangiogenic cytokines such as fractalkine/CX3CL1, CXCL16, interleukin (IL)-8/CXCL8, monocyte chemotactic protein 1 (MCP-1)/CCL2, epithelial neutrophil-activating protein 78 (ENA-78)/CXCL5 and vascular endothelial growth factor (VEGF) in 2-dGal treated HUVEC conditioned medium were measured by ELISA.

Results: Total glycans in RA serum were significantly higher than in NL serum [mean ± SEM; 477 ± 24 pmol/μl (n=10) and 339 ± 14 pmol/μl (n=10), p<0.05, respectively]. In addition, total glycans in RA serum were significantly decreased with tocilizumab treatment at 24 weeks. Total glycans in RA serum were also correlated with DAS28 (ESR). Percent of fucosylated proteins in total glycans were decreased with TCZ treatment at 24 weeks. 2-d Gal treated HUVEC tube formed towards RA synovial fluids (n=6 patients) were decreased compared with nontreated HUVEC tube formed (number of tube formed; 7 ± 1 and 25 ± 2, p<0.05, respectively). Fractalkine/CX3CL1, CXCL16, or IL-8/CXCL8 in 2-d Gal treated HUVEC conditioned medium were decreased compared with in non-treated HUVEC conditioned medium but not MCP-1/CCL2, ENA-78, or VEGF.

Conclusion: These data indicate that glycoproteins are involved with RA, and play a role in angiogenesis in RA and suggest that targeting glycosylation especially fucosylation may provide a method by which to decrease inflammation and potentially treat other inflammatory diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/inhibition-of-fucosylation-in-endothelial-cells-reduces-rheumatoid-arthritis-angiogenesis/