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Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin
J Wipff1, J Avouac, D Borderie
1Department of Rheumatology A, Paris Descartes University, Medical Faculty, Cochin Hospital, Paris, France.
Insights
This study found higher levels of soluble endoglin (sENG) in systemic sclerosis (SSc) patients, particularly those with vascular complications. These findings suggest sENG may be a useful biomarker for SSc vascular disease.
Area of Science:
- Vascular Biology
- Rheumatology
- Biomarker Discovery
Background:
- Systemic sclerosis (SSc) is a connective tissue disease marked by early microangiopathy and disrupted angiogenesis.
- Soluble endoglin (sENG), an anti-angiogenic protein, is implicated in vascular diseases like pre-eclampsia.
- Investigating sENG in SSc may reveal insights into its vascular pathology.
Purpose of the Study:
- To assess serum levels of soluble endoglin (sENG) in patients with systemic sclerosis (SSc).
- To evaluate sENG in relation to other vascular markers like VEGF and ADMA.
- To explore the association of sENG with clinical features of SSc.
Main Methods:
- Cross-sectional study involving 187 SSc patients and 48 controls.
- Serum sENG, VEGF, and ADMA levels measured using ELISA.
- Multivariate analysis to identify associations between sENG and clinical parameters.
Main Results:
- SSc patients exhibited significantly higher serum concentrations of sENG and VEGF compared to controls.
- Elevated sENG levels were associated with cutaneous ulcerations, ACA positivity, and impaired lung diffusion capacity in SSc patients.
- A negative correlation was observed between sENG and ADMA, but not between sENG and VEGF.
Conclusions:
- This study demonstrates elevated sENG levels in a large SSc cohort, linked to a distinct vascular phenotype.
- sENG emerges as a potential biomarker for vascular complications in SSc.
- Further research is needed to determine the predictive value and cellular mechanisms of sENG in SSc.
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.
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