title: Vascular endothelial growth factor and monocyte chemoattractant protein-1 in Behçet's patients with venous thrombosis.
abstract: OBJECTIVE
  Vascular lesions can involve both arterial and venous systems which are often the major causes complicating the disease course of Behçet's disease (BD). Vascular endothelial growth factor (VEGF) is a stimulant of angiogenesis secondary to ischemia while monocyte chemoattractant protein 1 (MCP-1) is induced by shear stresses leading to vascular collateral development. MCP-1 has been also shown to contribute to the recanalization of venous thrombi. Tumor necrosis factor-alpha (TNF-alpha) is known to play a major role in the pathogenesis of BD. Furthermore, up-regulation of secreted MCP-1 and VEGF was observed following stimulation with TNF-alpha. In view of the above functions of VEGF, MCP-1 and TNF-alpha, we hypothesized that these factors may be important in the pathogenesis of thrombosis seen in BD.
  
  
  METHODS
  A total of 36 patients with a diagnosis of BD were studied. BD patients were separated into 3 groups with respect to vascular involvement. Group BD-AT (n = 9) with acute thrombosis, BD-CT (n = 12) with chronic thrombosis and BD-MC (n = 15) with mucocutaneous involvement only. The control group (group H) was comprised of 20 healthy persons. In addition, patients with acute, DC-AT (n= 11) and patients with chronic DC-CT (n = 9) thrombosis without BD served as disease controls. Serum measurements of VEGF MCP-1 and TNF-alpha were performed by quantitative sandwich ELISA. The acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured.
  
  
  RESULTS
  The levels of VEGF were significantly higher in the patients in group BD-AT than either in group BD-CT or BD-MC (p = 0.03 and p < 0.001, respectively). However, no significant difference was found for VEGF levels of thrombotic patients regarding the cause (BD-AT vs. DC-AT, p = 0.063; BD-CT vs. DC-CT, p = 0.084) or the stage of thrombosis (DC-AT vs. DC-CT, p > 0.05). Both BD patients and disease controls with acute thrombosis had significantly higher levels of MCP-1 as compared to corresponding chronic thrombosis patients (BD-AT vs. DC-CT; p < 0.001; DC-AT vs. DC-CT, p < 0.001). Patients with BD and disease controls had significantly higher serum TNF-alpha level when compared with healthy subjects. No significant difference with respect to serum TNF-alpha level was noted when patient subgroups with BD and disease controls were compared with each other Serum levels of VEGF, MCP-1, and TNF-alpha were not found to be correlated with either ESR or CRP (p > 0.05).
  
  
  CONCLUSIONS
  Increased levels of VEGF and MCP-1 detected in BD thrombosis suggest the possible role of those angiogenic cytokines in the pathogenesis. Although not specific for BD, detection of VEGF or MCP-1 levels seems to serve as an assay for differentiation of BD patients with acute thrombosis from chronic.
authors.affiliation: Department of Internal Medicine, Gulhane Military School of Medicine, Ankara, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Bozoglu
authors.forename: A
authors.initials: A
authors.lastname: Dinc
authors.forename: H
authors.initials: H
authors.lastname: Erdem
authors.forename: S
authors.initials: S
authors.lastname: Pay
authors.forename: I
authors.initials: I
authors.lastname: Simsek
authors.forename: I H
authors.initials: IH
authors.lastname: Kocar
mesh_terms: D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000032:analysis; D000328:Adult; D001528:Behcet Syndrome / Q000097:blood* / Q000150:complications / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D005831:Genital Diseases, Female / Q000097:blood / Q000209:etiology / Q000473:pathology; D005832:Genital Diseases, Male / Q000097:blood / Q000209:etiology / Q000473:pathology; D006801:Humans; D008297:Male; D019226:Oral Ulcer / Q000097:blood / Q000209:etiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D020246:Venous Thrombosis / Q000097:blood* / Q000150:complications / Q000473:pathology
chemical_list: D000209:Acute-Phase Proteins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A