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

ObjectiveTo 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-α inhibitors.MethodsInflamed 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-naïve patients or after the beginning of a therapy with a TNF-α 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.ResultsIn the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (−44%; P = 0.003) in comparison to a delayed decrease in the TNF-α 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.ConclusionThe decrease of serum VEGF levels under treatment with glucocorticoids or TNF-α 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.