title: Correlation of biomarkers of endothelium dysfunction and matrix remodeling in patients with systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a multisystem disease characterized by microvascular dysfunction and excessive fibrosis. However, the relationship between these 2 features remains unclear. Endothelial dysfunction can be assessed by quantifying plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase. Matrix remodeling can be assessed by quantifying serum tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Both biomarkers are elevated in patients with SSc. Our objective was to test whether plasma ADMA is correlated with serum TIMP-1.
  
  
  METHODS
  We enrolled 91 subjects, 39 patients with SSc, 28 patients with primary Raynaud's phenomenon (RP), and 24 healthy volunteers. Plasma ADMA concentrations were measured by liquid chromatography-tandem mass spectrometry. Serum TIMP-1 concentrations were determined by ELISA.
  
  
  RESULTS
  Mean ADMA concentrations were higher in patients with SSc (0.68 microM +/- 0.12) than in patients with primary RP or healthy volunteers (respectively, 0.56 microM +/- 0.14 and 0.62 microM +/- 0.12; p = 0.002). Median serum TIMP-1 concentrations were increased in patients with SSc compared to primary RP and healthy volunteers [12 (9-15), 11 (8-13), and 10 (7-13) nM, respectively; p = 0.05]. In the SSc group, we observed a statistically significant correlation between plasma ADMA and serum TIMP-1 (r = 0.34, p = 0.035).
  
  
  CONCLUSIONS
  These data are consistent with our hypothesis of an association of endothelial dysfunction and matrix remodeling in scleroderma spectrum disorders.
authors.affiliation: Vascular MedicineDepartment, INSERM Clinical Research Center, Grenoble University Hospital, Grenoble, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Blaise
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Candice
authors.initials: C
authors.lastname: Trocme
authors.forename: Ghainsom D
authors.initials: GD
authors.lastname: Kom
authors.forename: Matthieu
authors.initials: M
authors.lastname: Roustit
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Carpentier
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Cracowski