title: Immature blood vessels in rheumatoid synovium are selectively depleted in response to anti-TNF therapy.
abstract: BACKGROUND
  Angiogenesis is considered an important factor in the pathogenesis of Rheumatoid Arthritis (RA) where it has been proposed as a therapeutic target. In other settings, active angiogenesis is characterized by pathologic, immature vessels that lack periendothelial cells. We searched for the presence of immature vessels in RA synovium and analyzed the dynamics of synovial vasculature along the course of the disease, particularly after therapeutic response to TNF antagonists.
  
  
  RESULTS
  Synovial arthroscopic biopsies from RA, osteoarthritis (OA) and normal controls were analyzed by double labeling of endothelium and pericytes/smooth muscle mural cells to identify and quantify mature/immature blood vessels. To analyze clinicopathological correlations, a cross-sectional study on 82 synovial biopsies from RA patients with variable disease duration and severity was performed. A longitudinal analysis was performed in 25 patients with active disease rebiopsied after anti-TNF-alpha therapy. We found that most RA synovial tissues contained a significant fraction of immature blood vessels lacking periendothelial coverage, whereas they were rare in OA, and inexistent in normal synovial tissues. Immature vessels were observed from the earliest phases of the disease but their presence or density was significantly increased in patients with longer disease duration, higher activity and severity, and stronger inflammatory cell infiltration. In patients that responded to anti-TNF-alpha therapy, immature vessels were selectively depleted. The mature vasculature was similarly expanded in early or late disease and unchanged by therapy.
  
  
  CONCLUSIONS
  RA synovium contains a significant fraction of neoangiogenic, immature blood vessels. Progression of the disease increases the presence and density of immature but not mature vessels and only immature vessels are depleted in response to anti-TNFalpha therapy. The different dynamics of the mature and immature vascular fractions has important implications for the development of anti-angiogenic interventions in RA.
authors: Servicio de Reumatología, Hospital 12 de Octubre, Madrid, Spain.
authors: Elena
authors: E
authors: Izquierdo
authors: Juan D
authors: JD
authors: Cañete
authors: Raquel
authors: R
authors: Celis
authors: Begoña
authors: B
authors: Santiago
authors: Alicia
authors: A
authors: Usategui
authors: Raimon
authors: R
authors: Sanmartí
authors: Manuel J
authors: MJ
authors: Del Rey
authors: José L
authors: JL
authors: Pablos
mesh_terms: D000199:Actins / Q000378:metabolism; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013583:Synovial Membrane / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D000199:Actins; D018501:Antirheumatic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha