Decreased ratio of circulatory vascular endothelial growth factor to endostatin in patients with systemic sclerosis--association with pulmonary involvement

Abstract

Objective: Vascular endothelial growth factor (VEGF) and endostatin appear to be involved in development of systemic sclerosis (SSc). We undertook this study to determine ratios of serum concentrations of VEGF to endostatin in SSc patients, healthy controls, assessments between cytokines, and lung-diffusing capacity (DLCO) as lung injury measurements related to interstitial lung disease (ILD).

Materials and methods: Serum VEGF and endostatin levels were measured with ELISA in 28 SSc patients (16 with lcSSc) and 20-matched healthy volunteers, evaluating correlation and balance. DLCO was corrected for hemoglobin, alveolar volume, and determined with a single breath technique.

Results: SSc serum concentrations (median; range) of endostatin were higher than controls (107.2; 13.6-261.2 vs. 77.8; 18.0-110.4 ng/ml, p < 0.05); VEGF levels did not differ (151.2; 4.5-836.4 vs. 286.4; 23.7-708.5 pg/ml, p < 0.05). Ratios of VEGF to endostatin were 2.6 and 3.6 times lower (p < 0.05) in SSc and dcSSc in comparison to healthy subjects. There were significant negative correlations between VEGF, endostatin in SSc (r = -0.51), and controls (r = -0.57). SSc with ILD (n = 20) had similar concentrations of VEGF, endostatin, and ratios of VEGF to endostatin compared to SSc alone. No correlations were seen between DLCO, VEGF, endostatin and their ratios in the whole SSc group. Negative correlations were noted between DLCO and VEGF (r = -0.82), with DLCO and the ratio of VEGF to endostatin (-0.62) in lcSSc with ILD (n = 10).

Conclusion: Decreased ratios of VEGF to endostatin may reflect imbalances between serum angiogenic, and anti-angiogenic activity in SSc, explaining impaired neoangiogenesis.