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.
Brakch
Noureddine
N
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
Dormond
Olivier
O
Bekri
Soumeya
S
Golshayan
Dela
D
Correvon
Magali
M
Mazzolai
Lucia
L
Steinmann
Beat
B
Barbey
Frédéric
F
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