Endothelial dysfunction is associated with decreased circulating endothelial progenitor cells in pateints with systemic cclerosis

Abstract

Background: The role of circulating bone marrow derived endothelial progenitor cells (EPCs) for vascular repair in scleroderma (SSc) remains unclear. Purpose: To examine endothelial dysfunction in SSc patients and to correlate findings with biochemical markers of endothelial injury, circulating EPC count, disease activity and organ involvement. Methods: Endothelial dependent and independent vasodilation responses were assessed by changes in flow mediated dilation (FMD%) and nitroglycerin challenge (NTG%) in the brachial artery respectively in SSc patients compared to age- and sex- matched controls. Serum levels of vascular endothelial growth factor (VEGF) and soluble vascular cell adhesion molecule (sVCAM)-1 were measured by ELISA. Enumeration of circulating CD133/VEGFR2+ EPCs was performed by flow cytometry. Results: Median FMD% (4.8% vs. 7.8%, P<0.001) and NTG% (17.0% vs. 21.4%, P=0.002) were found to be significantly lower in SSc patients (n=52) than controls (n=52), especially in patients with limited disease (lSSc). Median circulating EPC count was significantly lower in lSSc patients (23.0/ml) compared to controls (73.0/ml) (P<0.001). This was accompanied by higher level of sVCAM-1 in these patients compared to those with diffuse disease (P=0.01). Lower circulating EPC count was found to be associated with high disease activity (P=0.04), abnormal forced vital capacity (P=0.003), longer disease duration (P=0.04), total skin score>20 (P=0.03) and lSSc subset (P<0.001). Multivariate analysis identified disease duration as the only independent predictor for circulating EPC count (P=0.04). Conclusion: Endothelial dysfunction was demonstrated in SSc and correlated with biochemical markers of endothelial injury. Lower circulating EPCs might contribute to deficient vascular repair in SSc patients.