Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease.
OBJECTIVE
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.


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.


CONCLUSIONS
Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry disease.
Service of Angiology and Vascular Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 5 Rue Pierre Decker, 1011 Lausanne, Switzerland. frederic.barbey@chuv.ch
Noureddine
N
Brakch
Olivier
O
Dormond
Soumeya
S
Bekri
Dela
D
Golshayan
Magali
M
Correvon
Lucia
L
Mazzolai
Beat
B
Steinmann
Frédéric
F
Barbey
D000328:Adult; D000818:Animals; D001011:Aorta / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D017536:Carotid Artery, Common / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology; D000795:Fabry Disease / Q000097:blood* / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D020257:Ventricular Remodeling / Q000502:physiology*
D015415:Biomarkers; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine