title: Dysbalance of angiogenic and angiostatic mediators in patients with mixed connective tissue disease.
abstract: OBJECTIVE
  Vascular disease is common in mixed connective tissue disease (MCTD). The aim of the present study was to investigate, whether dysbalance of angiogenic and angiostatic factors occurs in MCTD.
  
  
  METHODS
  In all, 38 patients with MCTD, and 40 patients with systemic sclerosis (SSc) for comparison, were included. Four centres contributed to this cross-sectional analysis. A total of 66 healthy volunteers were used as controls. The serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin were determined by ELISA. For comparisons between controls and patients with MCTD and detection of associations of serum levels with dichotomous clinical parameters in patients with MCTD the Mann-Whitney test was used.
  
  
  RESULTS
  Serum levels of the angiogenic factor VEGF were significantly elevated in patients with MCTD and SSc. Significantly increased levels of the angiostatic factor endostatin were also detected in MCTD, but not in SSc. No differences were observed for bFGF. Levels of VEGF were higher in patients with MCTD with pulmonary arterial hypertension (PAH), acrosclerosis and myositis. In multivariate linear regression analysis, an additive model of PAH, myositis and lymphadenopathy accounted for 79% of the variability of the VEGF levels (r=0.889).
  
  
  CONCLUSIONS
  Molecular factors modulating angiogenic responses are dysregulated in patients with MCTD and SSc with increases of VEGF in MCTD and SSc and selective upregulation of endostatin in MCTD. Furthermore, high serum levels of VEGF might characterise patients with MCTD with a more severe course of the disease with increased prevalence of PAH and myositis.
authors.affiliation: Department of Internal Medicine, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Germany. joerg.distler@uk-erlangen.de
authors.forename: Jörg H W
authors.initials: JH
authors.lastname: Distler
authors.forename: Tobias
authors.initials: T
authors.lastname: Strapatsas
authors.forename: Dörte
authors.initials: D
authors.lastname: Huscher
authors.forename: Clara
authors.initials: C
authors.lastname: Dees
authors.forename: Alfiya
authors.initials: A
authors.lastname: Akhmetshina
authors.forename: Hans P
authors.initials: HP
authors.lastname: Kiener
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Tarner
authors.forename: Britta
authors.initials: B
authors.lastname: Maurer
authors.forename: Marcel
authors.initials: M
authors.lastname: Walder
authors.forename: Beat
authors.initials: B
authors.lastname: Michel
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D043169:Endostatins / Q000097:blood*; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000097:blood* / Q000150:complications; D009220:Myositis / Q000097:blood / Q000209:etiology; D012595:Scleroderma, Systemic / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D043169:Endostatins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2