SR 25989 inhibits healing of a mechanical wound of confluent human saphenous vein endothelial cells which is modulated by standard heparin and growth factors.
The thienopyridine, ticlopidine, a potent platelet antiaggregating agent and SR 25989, an esterified derivative of ticlopidine, devoid of antiplatelet activity, were tested in an in vitro model of healing of a mechanical wound in confluent endothelium. This model allows exploration of substances involved in wound healing and angiogenesis. These two compounds inhibited both cell proliferation and cell migration during lesion repair in a dose-dependent manner (18-150 microM), SR 25989 being twice as active as ticlopidine. Its effect was not inhibited by acidic or basic fibroblast growth factor or by platelet derived growth factor. In contrast, it exerted a conjugated inhibition with standard heparin and was able to totally reverse the healing increase induced by a mixture of acidic fibroblast growth factor and heparin. The mechanism of action of SR 25989 is not yet elucidated, but it does not seem to involve competition with fibroblast growth factors since these substances were not able to alter their binding to receptors on the endothelial cell surface. SR 25989 therefore appears as a promising new candidate for inhibition of angiogenesis.
Klein-Soyer
C
C
INSERM U.311, Centre Régional de Transfusion Sanguine, Strasbourg, France.
Cazenave
J P
JP
Herbert
J M
JM
Maffrand
J P
JP
D002455:Cell Division; D002478:Cells, Cultured; D000077144:Clopidogrel; D003470:Culture Media; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009389:Neovascularization, Pathologic; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D003470:Culture Media; D010975:Platelet Aggregation Inhibitors; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine