Journal
ARTHRITIS RESEARCH & THERAPY
Volume 19, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13075-017-1271-7
Keywords
Systemic sclerosis; Fractalkine; Endothelial progenitor cells; Endothelial microparticles; Circulating endothelial cells; Vascular endothelial growth factor; Endothelin-1; Endothelial homeostasis
Categories
Funding
- Assistance Publique-Hopitaux de Marseille Appel d'Offre de Recherche Clinique (AORC) [2011-A00095-35]
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Background: The disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity. Methods: We conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34(+) progenitor cell subsets. Colony-forming unit-endothelial cells (CFU-ECs) were counted by culture assay. Circulating endothelial cells were enumerated using anti-CD146-based immunomagnetic separation. Blood levels of endothelin-1, vascular endothelial growth factor (VEGF) and soluble fractalkine (s-Fractalkine) were evaluated by enzyme-linked immunosorbent assay. Disease-associated markers were identified using univariate, correlation and multivariate analyses. Results: Enhanced numbers of EMPs, CFU-ECs and non-haematopoietic CD34(+)CD45(-) endothelial progenitor cells (EPCs) were observed in patients with SSc. Patients with SSc also displayed higher serum levels of VEGF, endothelin-1 and s-Fractalkine. s-Fractalkine levels positively correlated with CD34(+)CD45(-) EPC numbers. EMPs, s-Fractalkine and endothelin-1 were independent factors associated with SSc. Patients with high CD34(+)CD45(-) EPC numbers had lower forced vital capacity values. Elevated s-Fractalkine levels were associated with disease severity, a higher frequency of pulmonary fibrosis and altered carbon monoxide diffusion. Conclusions: This study identifies the mobilisation of CD34(+)CD45(-) EPCs and high levels of s-Fractalkine as specific features of SSc-associated vascular activation and disease severity. This signature may provide novel insights linking endothelial inflammation and defective repair processes in the pathogenesis of SSc.
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