Rheumatology Advance Access published online on June 23, 2009
Rheumatology, doi:10.1093/rheumatology/kep154
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The transport of high amounts of vascular endothelial growth factor by blood platelets underlines their potential contribution in systemic sclerosis angiogenesis
1Inserm U 889, IFR 66,2ISPED, Bordeaux University, Bordeaux,3Internal Medicine Department, Amiens University Hospital, Amiens,4Internal and Vascular Medicine Department,5Internal Medicine Department A and 6Platelet Diseases Reference Centre, IFR 4, Bordeaux University Hospital, Bordeaux, France.
Correspondence to:
Jean Ripoche, Inserm U889, 146, rue Léo Saignat, 33076, Bordeaux, France. E-mail: jean.ripoche{at}u-bordeaux2.fr
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Abstract |
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Objectives. Altered angiogenesis is a characteristic feature in SSc and remains ill-understood. VEGF is believed to play a central role. Serum VEGF is elevated in SSc patients but questions remain concerning the source of circulating VEGF. Here we investigated platelet activation and the role of platelets as a source of VEGF and other angiogenic mediators in this disease.
Methods. A cohort of 40 patients with SSc was included. Age- and sex-matched healthy subjects and subjects presenting a primary RP were included as controls. Platelets were isolated, activated with thrombin and the secretion of VEGF, platelet derived growth factor, homodimeric form BB (PDGF-BB), TGF-β1 and angiopoietins-1 and -2 measured. Plasma concentrations of these mediators and the functionality of platelet-derived VEGF were also studied. Platelet activation was assayed by measuring plasma β-thromboglobulin and expression of P-selectin on platelets. The effect of iloprost on VEGF secretion by platelets was studied.
Results. Platelets from SSc patients, in contrast to controls, secreted large amounts of VEGF when activated, but not PDGF-BB, TGF-β1 or angiopoietins. Increased expression of membrane P-selectin confirmed platelet activation in the patients. Iloprost inhibited VEGF secretion by platelets both in vivo and in vitro, through inhibition of platelet activation.
Conclusions. Platelets transport high levels of VEGF in SSc. They may contribute to circulating VEGF because of ongoing activation in the course of the disease. If activated at the contact of injured endothelium, platelets may be important in the altered angiogenesis associated with the disease through the secretion of high levels of VEGF.
KEY WORDS: Systemic sclerosis, Blood platelets, Vascular endothelial growth factor
*Anne Solanilla and Julien Villeneuve equally contributed to this work.
Submitted 31 December 2008; Accepted 14 May 2009