Inhibitory Effects of a Novel Antiplatelet Agent, E5510, on Collagen-Induced Platelet-Derived Growth Factor Release and Aggregation of Human Platelets In Vitro.

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E5510, 4-cyano-5, 5-bis(4-methoxyphenyl)-4-pentenoic acid, is a new anti-platelet-aggregation agent under development. We examined the inhibitory efficacy of E5510 on PDGF-release from washed human platelets. E5510 concentration-dependently inhibited collagen-induced PDGF release from human platelets. PDGF release was reduced to below the detection limit (0.47 ng/ml) by preincubation of platelets with 0.04 μM or higher concentrations of E5510. Total growth factor release from platelets was also measured by a bioassay with cultured smooth muscle cells. E5510 almost completely abolished the mitogenic effect of collagen-induced platelet releasates at concentrations of 0.04 μM or higher. Our data suggest that the release of PDGF and other growth factors was inhibited by E5510 at the same concentration that inhibited platelet aggregation.
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