Correlation of biomarkers of endothelium dysfunction and matrix remodeling in patients with systemic sclerosis.
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.
Blaise
Sophie
S
Vascular MedicineDepartment, INSERM Clinical Research Center, Grenoble University Hospital, Grenoble, France.
Maas
Renke
R
Trocme
Candice
C
Kom
Ghainsom D
GD
Roustit
Matthieu
M
Carpentier
Patrick H
PH
Cracowski
Jean-Luc
JL