Abnormalities in the Regulators of Angiogenesis in Patients with Scleroderma

Abstract

Objective.To determine plasma levels of regulators of angiogenesis in patients with scleroderma and to correlate those levels with manifestations of scleroderma-related vascular disease.Methods.Plasma levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor-2 (FGF-2), matrix metalloproteinase-9 (MMP-9), endostatin, pro-MMP-1, hepatocyte growth factor (HGF), placental growth factor (PlGF), and FGF-4 were examined by ELISA in a cross-sectional study of 113 patients with scleroderma and 27 healthy controls. Simple and multivariate regression models were used to look for associations between factor levels and clinical disease characteristics.Results.There were marked differences in the levels of pro-angiogenic growth factors between patients with scleroderma and controls, with significant elevations of VEGF, PDGF, FGF-2, and PlGF among patients with scleroderma (p < 0.0001). Levels of MMP were also higher in scleroderma patients compared to controls (MMP-9 and pro-MMP-1) (p < 0.0001). Levels of the pro-angiogenic and anti-fibrotic factor, HGF, were noted to be lower in patients with scleroderma, but had a positive correlation with right ventricular systolic pressure (RVSP) as measured by echocardiogram (p < 0.0001) and the Raynaud Severity Score (p = 0.05). Endostatin (an anti-angiogenic factor) was notably higher in patients with scleroderma (p < 0.0001) and also correlated positively with RVSP (p = 0.023).Conclusion.These results demonstrate striking abnormalities in the circulating regulators of angiogenesis in patients with scleroderma. The levels of some factors correlate with measures of vascular disease among patients with scleroderma. Dysregulated angiogenesis may play a role in the development of scleroderma vascular disease.