Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin.
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.


CONCLUSIONS
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.
Wipff
J
J
Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, Paris, France.
Avouac
J
J
Borderie
D
D
Zerkak
D
D
Lemarechal
H
H
Kahan
A
A
Boileau
C
C
Allanore
Y
Y
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D000071063:Endoglin; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology*; D011956:Receptors, Cell Surface / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications*; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C018524:N,N-dimethylarginine; D001120:Arginine