Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease
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Noureddine Brakch1, Olivier Dormond, Soumeya Bekri
1Service of Angiology and Vascular Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 5 Rue Pierre Decker, 1011 Lausanne, Switzerland. frederic.barbey@chuv.ch
Insights
Sphingosine-1 phosphate (S1P) is identified as a growth factor in Fabry disease plasma, contributing to cardiovascular remodelling. Elevated S1P levels correlate with disease severity, suggesting therapeutic potential.
Area of Science:
- Cardiovascular Biology
- Lysosomal Storage Disorders
- Biochemistry
Background:
- Fabry disease is characterized by left-ventricular hypertrophy and arterial intima-media thickening.
- Pathogenesis is linked to a circulating growth-promoting factor in plasma.
Purpose of the Study:
- To identify the growth-promoting factor in the plasma of Fabry disease patients.
- To investigate the role of this factor in cardiovascular remodelling.
Main Methods:
- Classical biochemical purification strategy.
- Quantification of plasma sphingosine-1 phosphate (S1P) levels via ELISA.
- Correlation analysis with cardiovascular parameters.
- Experimental validation in a mouse model.
Main Results:
- Sphingosine-1 phosphate (S1P) was isolated and identified as a proliferative factor.
- Plasma S1P levels were significantly elevated in Fabry disease patients compared to controls.
- S1P levels correlated positively with intima-media thickness and left-ventricular mass index.
- S1P administration induced cardiovascular remodelling in mice.
Conclusions:
- Sphingosine-1 phosphate plays a role in cardiovascular remodelling associated with Fabry disease.
- Findings suggest S1P as a potential therapeutic target for cardiovascular complications in Fabry disease.
Aims:
A hallmark of Fabry disease is the concomitant development of left-ventricular hypertrophy and arterial intima-media thickening, the pathogenesis of which is thought to be related to the presence of a plasmatic circulating growth-promoting factor. We therefore characterized the plasma of patients with Fabry disease in order to identify this factor.
Methods And Results:
Using a classical biochemical strategy, we isolated and identified sphingosine-1 phosphate (S1P) as a proliferative factor present in the plasma of patients with Fabry disease. Plasma S1P levels were significantly higher in 17 patients with Fabry disease compared with 17 healthy controls (225 +/- 40 vs. 164 +/- 17 ng/mL; P = 0.005). There was a positive correlation between plasma S1P levels and both common carotid artery intima-media thickness and left-ventricular mass index (r(2) = 0.47; P = 0.006 and r(2) = 0.53; P = 0.0007, respectively). In an experimental model, mice treated with S1P developed cardiovascular remodelling similar to that observed in patients with Fabry disease.
Conclusion:
Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry disease.
