Roberto Giacomelli, Italy
University of Rome "campus biomedico School of medicinePresenter of 4 Presentations
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ANGIOGENESIS PLAYS A MAJOR ROLE IN PANNUS FORMATION AND ORGANIZATION DURING RHEUMATOID ARTHRITIS
Abstract
Background and Aims
During rheumatoid arthritis (RA), the angiogenic processes, occurring during pannus-formation, may be a new therapeutic target. JAK/STAT pathways may play a role during angiogenesis and the aim of this work was to investigate the inhibiting role of a selective JAK inhibitor, tofacitinib, on the angiogenic mechanisms occuring during RA.
Methods
After ethical approval, Jak1/3 and Stat1/3 expression was evaluated on 5 RA-synovial-tissues and 5 healthy-synovial-tissues. In vitro, ECs, stimulated with VEGF and/or tofacitinib, were assessed for tube formation, migration and proliferation, by matrigel and Boyden chamber assay and by ki67 gene-expression. In vivo, 32 mice received collagen (CIA) and 32 mice PBS (control). At day-19, CIA and controls mice were divided in 16 mice receiving vehicle and 16 mice receiving tofacitinib. At day-35, the arthritis score, the thickness of paw joints and the serum levels of VEGF and Ang-2 were evaluated.
Results
The expression of JAK-1/3, STAT-1/3 in synovial tissue of RA-patients were significantly higher than HC. In vitro, after tofacitinib-treatment, HC-ECs lose their ability to form vessels, to proliferate and to migrate. In vivo, administration of tofacitinib prevented the increase of the arthritis score, the paw thickness, the synovial vessels and VEGF and Ang-2 serum-accumulation, when compared to CIA without tofacitinib.
Conclusions
We explored the anti-angiogenic role of tofacitinib, reporting its ability to inhibit in vitro the angiogenesis mechanisms of ECs, and in vivo the formation of new synovial vessels, occurring during experimental arthritis. These findings could open new therapeutic perspective by using tofacitinib in RA.