Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin

• Published in: Rheumatology (Oxford, England) England), 2008-07, Vol.47 (7), p.972-975
• Main Authors: Wipff, J., Avouac, J., Borderie, D., Zerkak, D., Lemarechal, H., Kahan, A., Boileau, C., Allanore, Y.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - blood; Arginine - analogs & derivatives; Arginine - blood; Asymmetric dimethylarginine; Biological and medical sciences; Biomarkers - blood; Cross-Sectional Studies; Diseases of the osteoarticular system; Endoglin; Female; Humans; Male; Medical sciences; Middle Aged; Neovascularization, Pathologic - blood; Neovascularization, Pathologic - etiology; Receptors, Cell Surface - blood; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma, Systemic - blood; Scleroderma, Systemic - complications; Solubility; Soluble endoglin; Soluble vascular endothelial growth factor; Systemic sclerosis; Vascular Endothelial Growth Factor A - blood
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ken100

Objective. SSc is a CTD characterized by early generalized microangiopathy with disturbed angiogenesis. Soluble endoglin (sENG), a serum anti-angiogenic protein, has recently been described as a major actor in pre-eclampsia, another severe vascular disease with abnormal angiogenesis. The aim of this study was to investigate, in a cross-sectional study, sENG levels together with other serum vascular markers. Methods. Serum levels of sENG were assessed by ELISA in consecutive SSc patients and controls matched for age and sex. We also measured by ELISA serum levels of VEGF and asymmetric dimethylarginine (ADMA), as respective markers of angiogenesis and endothelial dysfunction. Results. We included 235 unrelated subjects: 187 SSc patients and 48 controls. Higher concentrations of sENG (P = 0.002) and sVEGF (P < 0.0001) were found in SSc patients compared with controls whereas there was no difference for ADMA. In multivariate analysis, sENG levels were significantly increased in SSc patients with cutaneous ulcerations (P = 0.0003), positive for ACAs (P = 0.009) and with abnormal diffusing capacity for carbon monoxide divided by alveolar volume (P = 0.03). Soluble ENG levels negatively correlated with ADMA, but no relationship was found between sENG and sVEGF. Conclusion. This study shows increased values of sENG in a large SSc cohort and a relevant association with a vascular phenotype. The predictive value of the biomarker sENG and its potential role on cellular endothelial disturbances remain to be determined.