Background/Purpose: While common pathogenic mechanisms exist between PsA and RA, distinct vascular morphology has been observed, with PsA displaying a tortuous, dilated, irregular shaped morphology compared to a straight regular branching pattern observed in RA. The aim of this study is to examine the effect of the PsA and RA joint microenvironment on endothelial cell function.

Methods: PsA and RA patients underwent key-hole joint arthroscopy and synovial biopsies were obtained. PsA and RA synovial fibroblasts (FLS) were isolated and grown to passage 1-5. PsA and RA FLS supernatants were harvested and referred to as conditioned media (CM). Endothelial cells (EC) were cocultured with PsA FLS/RA FLS or PsA CM/RA CM, and pro-inflammatory mediators (cytokines, matrix-metalloproteinases, angiogenic growth factors, chemokines and adhesion molecules) were quantified by ELISA, real-time PCR and flow cytometry.

Results: Co-culture of PsA and RA FLS with EC induced IL-6 secretion, with no effect observed for MCP-1 or Ang2. PsA FLS CM induced MCP-1, Ang2, ICAM-1, MMP2 and MMP3 expression in EC, with only MMP-2 increasing in response to RA FLS CM. Both PsA FLS CM and RA FLS CM decreased VCAM-1 expression, an effect that was more pronounced for RA FLS CM. Either co-culture of PsA FLS/RA FLS or PsA FLS CM/RA FLS CM with EC induced the frequency and/or MFI of key chemokine receptors CXCR3 and CXCR4 on EC, an effect that was more pronounced for FLS CM vs FLS co-culture, particularly for PsA CM. Both PsA FLS/RA FLS coculture or PsA/RA CM decreased the frequency of CXCR5, however induced CXCR5 MFI. Only co-culture with PsA FLS and RA FLS induced the expression of ICAM-1, with no effect observed for PsA or RA FLS CM. No effect was observed for VCAM-1 expression. In contrast, the effect of coculture on FLS led to a reduction in the expression of ICAM-1 on both PsA and RA FLS, with increased expression of VCAM-1 observed for PsA FLS. No effect was observed for chemokine receptor expression on either PsA FLS or RA FLS when co-cultured with EC.

Conclusion: PsA and RA FLS/CM induce angiogenic, chemokine and adhesion molecule expression on EC, with differential effects for some mediators observed in response to PsA vs RA joint microenvironments. Furthermore, differences were observed between EC-FLS cocultures vs EC FLS CM co-cultures, suggesting cell-cell contact and soluble mediators both influence the EC pathogenic phenotype.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-the-inflamed-joint-microenvironment-on-endothelial-cell-function/