title: Angiogenesis is increased in advanced haemophilic joint disease and characterised by normal pericyte coverage.
abstract: BACKGROUND
  Repeated intra-articular bleedings in patients with haemophilia results in a crippling arthropathy for which no specific treatment is currently available. Recent studies have shown that neoangiogenesis is involved in the pathologic process. The aim of this study was to determine whether angiogenesis is dysregulated in haemophilic joint disease (HJD).
  
  
  METHODS
  Synovial tissue and synovial fluid were collected from patients with severe haemophilia undergoing knee or hip replacement and from a control group consisting of non-haemophilic patients undergoing diagnostic procedures. In a second set of patients, blood samples were collected in patients with mild, moderate and severe haemophilia A when free from current bleeding. Analysis of microvascular density, vascular endothelial growth factor (VEGF) expression and pericyte coverage was performed by immunofluorescence. Analyses of VEGF concentrations in plasma, platelet lysates and synovial fluid were performed by ELISA.
  
  
  RESULTS
  Microvascular density and VEGF expression were significantly increased in synovial tissue from haemophilic patients compared with controls (P = 0.005 and P = 0.02, respectively). There was no difference in pericyte coverage of synovial vessels or levels of VEGF in plasma, platelet lysates or synovial fluid.
  
  
  CONCLUSIONS
  Angiogenesis observed as synovial microvascular density, and VEGF expression is increased in HJD. As pericyte coverage was similar in synovial vessels from haemophilic and non-haemophilic patients, we assume that the vessels were mature, suggesting that the rate of new vessel formation is low in the chronic phase of haemophilic joint disease.
authors.affiliation: Coagulation Unit, Haematology Centre, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Department of Haematology and Coagulation, Skåne University Hospital, Malmö, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Zetterberg
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.forename: Rickard
authors.initials: R
authors.lastname: Wallensten
authors.forename: Massimo
authors.initials: M
authors.lastname: Morfini
authors.forename: Daniela
authors.initials: D
authors.lastname: Melchiorre
authors.forename: Margareta
authors.initials: M
authors.lastname: Holmström
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology; D005260:Female; D006467:Hemophilia A / Q000378:metabolism*; D006801:Humans; D007592:Joint Diseases / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D020286:Pericytes / Q000166:cytology*; D013582:Synovial Fluid / Q000166:cytology; D013583:Synovial Membrane / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; haemophilia; joint; pericyte; platelet; vascular endothelial growth factor