title: Imbalance in production between vascular endothelial growth factor and endostatin in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To clarify whether synovial cell proliferation indicates an imbalance in production between angiogenic growth factors and angiogenesis inhibitors in rheumatoid arthritis (RA), we investigated the production of basic fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF) as representative angiogenic growth factors and endostatin as a representative angiogenesis inhibitor.
  
  
  METHODS
  The b-FGF, VEGF, and endostatin levels in 90 samples of peripheral blood (PB) and 15 samples of joint fluid obtained from patients with RA and 30 samples of PB and 10 samples of joint fluid from patients without RA, including 20 patients with inflammatory arthritis without purulent arthritis, and 10 patients with osteoarthritis were measured by ELISA. VEGF and endostatin levels in blood samples from 22 patients with RA were measured at 2 points: before and 4 or 5 months after the commencement of medication.
  
  
  RESULTS
  The b-FGF and VEGF levels in the PB and joint fluid samples from patients with RA were markedly elevated compared to samples from patients without RA. In contrast, endostatin levels in PB and joint fluid samples from patients with RA were almost the same as in the samples from patients without RA. VEGF levels in blood samples obtained 4 or 5 months after the commencement of medication (combination of prednisolone 5 mg/day and disease modifying antirheumatic drugs: either bucillamine 100 mg/day or salazosulfapyridine 1,000 mg/day) were significantly decreased from 27.1 +/- 8.5 pg/ml in samples obtained before commencement of medication to 18.1 +/- 16.2 pg/ml. Endostatin levels in the corresponding samples were significantly increased, from 31.5 +/- 7.0 to 57.1 +/- 22.8 ng/ml [correction].
  
  
  CONCLUSIONS
  Our results reveal significant differences in b-FGF and VEGF levels in PB and joint fluid samples, but no difference in endostatin levels, between patients with RA and those without RA, suggesting that angiogenesis in RA occurs as a result of an imbalance in production between angiogenic growth factors and angiogenesis inhibitors.
authors.affiliation: Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan. Nagashima_Masakazu/rheum@nms.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nagashima
authors.forename: G
authors.initials: G
authors.lastname: Asano
authors.forename: S
authors.initials: S
authors.lastname: Yoshino
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011239:Prednisolone / Q000627:therapeutic use; D012460:Sulfasalazine / Q000627:therapeutic use; D013582:Synovial Fluid / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D012460:Sulfasalazine; D003094:Collagen; D011239:Prednisolone; D003545:Cysteine; C026535:bucillamine