sphingosine-1-phosphate and Hypertrophy--Left-Ventricular

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.. 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.. Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry disease.

Topics: Adult; Animals; Aorta; Biomarkers; Carotid Artery, Common; Cell Proliferation; Cells, Cultured; Endothelium, Vascular; Fabry Disease; Female; Humans; Hypertrophy, Left Ventricular; Lysophospholipids; Male; Mice; Middle Aged; Muscle, Smooth, Vascular; Rats; Rats, Wistar; Sphingosine; Tunica Intima; Tunica Media; Ventricular Remodeling