Linking systemic angiogenic factors (VEGF, angiogenin, TIMP-2) and Doppler ultrasound to anti-inflammatory treatment in rheumatoid arthritis

Objective: To evaluate an association between synovial Doppler flow and serum levels of vascular endothelial growth factor (VEGF), angiogenin and TIMP-2 in patients with rheumatoid arthritis during anti-inflammatory treatment with glucocorticoids and TNF-alpha inhibitors. Methods: Inflamed wrists of 15 patients with rheumatoid arthritis (RA) were examined by two independent ultrasound investigators prior to and at days 3, 7, 14 and 42 after the initiation of treatment with glucocorticoids in therapy-naive patients or after the beginning of a therapy with a TNF-alpha inhibitor in patients with DMARD failure. Quantitative three-dimensional power Doppler ultrasonographic assessment of synovial vascularization was compared at each visit with serum levels of VEGF, angiogenin and TIMP-2. Results: In the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (-44%; P = 0.003) in comparison to a delayed decrease in the TNF-alpha inhibitor group after 6 weeks (-46%; P = 0.001). A significant reduction of serum VEGF levels could be determined with a delay of 1 week after the decrease of Doppler activity but no correlation was found between both parameters (rho: P = 0.7; r = -0.03). Angiogenin concentrations decreased in the TNF group and increased in the GC group. Levels of TIMP-2 did not change significantly in both groups. Conclusion: The decrease of serum VEGF levels under treatment with glucocorticoids or TNF-alpha inhibitors followed the reduction of the intra-articular synovial Doppler flow. This result supports the idea that the reduction of synovial perfusion due to anti-inflammatory treatment is not regulated by systemic VEGF, but that the inflamed joints are the source for circulating VEGF. (C) 2012 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.