The transport of high amounts of vascular endothelial growth factor by blood platelets underlines their potential contribution in systemic sclerosis angiogenesis.
OBJECTIVE
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-beta1 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 beta-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-beta1 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.
Solanilla
Anne
A
Inserm U889, IFR 66, Bordeaux, France.
Villeneuve
Julien
J
Auguste
Patrick
P
Hugues
Michel
M
Alioum
Ahmadou
A
Lepreux
Sébastien
S
Ducroix
Jean-Pierre
JP
Duhaut
Pierre
P
Conri
Claude
C
Viallard
Jean-François
JF
Nurden
Alan T
AT
Constans
Joël
J
Ripoche
Jean
J
D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D000077214:Becaplermin; D001692:Biological Transport / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D009389:Neovascularization, Pathologic / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011446:Prospective Studies; D020574:Proto-Oncogene Proteins c-sis; D012595:Scleroderma, Systemic / Q000097:blood*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000502:physiology
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D016285:Iloprost