title: Linking systemic angiogenic factors (VEGF, angiogenin, TIMP-2) and Doppler ultrasound to anti-inflammatory treatment in rheumatoid arthritis.
abstract: 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-α 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-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.
  
  
  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-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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Krankenhaus Porz am Rhein, Abteilung für Rheumatologie, Urbacher Weg 19, 51149 Köln, Germany. j.strunk@khporz.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Strunk
authors.forename: Carola
authors.initials: C
authors.lastname: Rumbaur
authors.forename: Katinka
authors.initials: K
authors.lastname: Albrecht
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012259:Ribonuclease, Pancreatic / Q000097:blood*; D013583:Synovial Membrane / Q000000981:diagnostic imaging / Q000187:drug effects; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D018608:Ultrasonography, Doppler; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014955:Wrist Joint / Q000000981:diagnostic imaging / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; C560823:TIMP2 protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic