title: Vascular endothelial growth factor production in polymyalgia rheumatica.
abstract: OBJECTIVE
  To evaluate peripheral production and synovial expression of vascular endothelial growth factor (VEGF) in polymyalgia rheumatica (PMR).
  
  
  METHODS
  Circulating levels of VEGF in PMR (serum concentration and in vitro release by peripheral blood mononuclear cells [PBMC]) were investigated by enzyme-linked immunosorbent assay. Local expression of VEGF in shoulder synovial tissue was investigated by immunohistochemical analysis. Investigations were performed in patients with active, untreated disease and in patients treated with corticosteroids.
  
  
  RESULTS
  VEGF serum concentrations were significantly higher in untreated PMR patients than in normal control subjects. During steroid treatment, VEGF serum concentrations reached their lowest level after the sixth month of treatment. PBMC isolated from untreated PMR patients spontaneously secreted a higher amount of VEGF compared with PBMC from control subjects. Corticosteroid therapy did not affect the ability of PBMC to produce VEGF. Immunohistochemical staining performed on shoulder synovial tissue showed VEGF expression in both the lining layer and the sublining area. In 3 of 4 treated patients, no VEGF staining was found in synovial tissue during corticosteroid therapy. VEGF expression correlated with vessel density, but was not associated with alphavbeta3 and alphavbeta5 integrin expression.
  
  
  CONCLUSIONS
  Peripheral and local VEGF releases have different responses to steroid treatment in PMR. The lack of response to corticosteroids by peripheral VEGF production supports the hypothesis that systemic involvement is dominant in PMR. At the synovial level, VEGF production is linked to vascular proliferation and is thus directly involved in the pathogenesis of synovitis.
authors.affiliation: University of Bologna, and Istituti Ortopedici Rizzoli, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Meliconi
authors.forename: L
authors.initials: L
authors.lastname: Pulsatelli
authors.forename: P
authors.initials: P
authors.lastname: Dolzani
authors.forename: L
authors.initials: L
authors.lastname: Boiardi
authors.forename: P
authors.initials: P
authors.lastname: Macchioni
authors.forename: C
authors.initials: C
authors.lastname: Salvarani
authors.forename: T
authors.initials: T
authors.lastname: Silvestri
authors.forename: L
authors.initials: L
authors.lastname: Frizziero
authors.forename: A
authors.initials: A
authors.lastname: Facchini
mesh_terms: D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000097:blood; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis* / Q000097:blood; D011111:Polymyalgia Rheumatica / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis; D013583:Synovial Membrane / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D016023:Integrins; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors