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 age nt and SR 25989, an esterified derivative of ticlopidine, devoid of an tiplatelet activity, were tested in an in vitro model of healing of a mechanical wound in confluent endothelium. This model allows explorati on 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 mu M), SR 25989 bein g twice as active as ticlopidine. Its effect was not inhibited by acid ic or basic fibroblast growth factor or by platelet derived growth fac tor. In contrast, it exerted a conjugated inhibition with standard hep arin 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 substan ces were not able to alter their binding to receptors on the endotheli al cell surface. SR 25989 therefore appears as a promising new candida te for inhibition of angiogenesis. (C) 1994 Wiley-Liss, Inc.