Background/Purpose: Angiogenesis is an essential component in the pathogenesis of psoriatic arthritis (PsA). Extracellular matrix metalloproteinase inducer (EMMPRIN) is a multifunctional protein that can enhance angiogenesis by inducing vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs).

Objectives: (a) To assess the concentrations of angiogenic factors in serum of PsA patients in comparison to rheumatoid arthritis (RA) patients and healthy controls. (b) To evaluate the role of EMMPRIN as a mediator of fibroblast-macrophage interactions and angiogenesis in vitro.

Methods: Blood samples were collected from 56 PsA patients with active disease, 41 PsA patients in remission, 33 active RA patients and 33 healthy individuals. Serum levels of EMMPRIN, VEGF, MMP-9, MMP-7, MMP-3, MMP-2, and MMP-14 were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The secreted concentrations of EMMPRIN, VEGF and MMP-9 in a co-culture system of fibroblast (HT1080) and monocyte cell lines (U937 and MonoMac6) were compared to each single cell culture using ELISA. The role of EMMPRIN was demonstrated by the addition of a blocking anti-EMMPRIN antibody to the co-culture. Supernatants derived from single or co-cultures, with or without the addition of anti-EMMPRIN, were applied onto human EaHy926 endothelial cells that were seeded on matigel® to assess the pro-angiogenic potential of EMMPRIN on tube formation.Statistical analysis: Multiple groups were compared using the one-way ANOVA followed by Bonferrroni’s multiple comparison post-hoc test, and two groups were compared using the two-tailed unpaired student t test. P values exceeding 0.05 were not considered significant.

Results: PsA patients had significantly elevated levels of serum EMMPRIN, MMP-7, MMP-14 compared to RA patients (p<0.001, p<0.01 p<0.01, respectively) and to controls (p<0.0001 p<0.01, p<0.01 respectively). The levels of VEGF (p<0.05), MMP-14 (p<0.05), MMP-3 (p<0.0001) were higher in PsA patients with active disease compare to patients in remission. MMP-2 levels were significantly higher in both PsA and RA groups compared to controls (p<0.0001). Serum concentrations of MMP-9 were significantly lower in RA and PsA patients compared to controls (p<0.0001), but no significant difference was noted between the two disease groups.

Secretion of EMMPRIN, VEGF and MMP-9 were synergistically enhanced in the co-culture (p<0.01 for the three proteins relative to each of the single cultures). The addition of the blocking anti-EMMPRIN antibody reduced the level of VEGF (1.7-folds, p<0.001) and MMP-9 (1.4-folds, p<0.001) in the co-culture. Higher number of closed lumens were generated when EaHy926 cells were incubated with supernatants from co-cultured relative to each single culture (p<0.05). This number significantly decreased (p<0.05) when EMMPRIN was blocked by anti-EMMPRIN antibody.

Conclusion: Our results collectively implicate EMMPRIN as a mediator of fibroblasts-monocytes interactions that regulates angiogenesis, and suggest it may play an important role in the pathogenesis of PsA

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-extracellular-matrix-metalloproteinase-inducer-emmprin-in-the-pathogenesis-of-psoriatic-arthritis/