E5510 antagonizes thrombin receptor signals by inhibiting NF-kappa B activation

We have recently demonstrated that NF-kappa B is involved in a thrombin-signaling and that the antisense oligodeoxynucleotides (ODNs) of NF-kappa B has a marked inhibitory effect on thrombin-induced cellular responses. In this study, we demonstrate that E5510 (4-cyano-5,5-bis(methoxyphenyl)-4-pentenoic acid), a compound with anti-platelet activity preferentially inhibits the thrombin-inducible NF-kappa B activation and then antagonizes the following thrombin-induced cellular responses, proliferation and cytokines production in vascular smooth muscle cell, and the adherency of differentiated HL-60 cells. These data suggest that E5510 is an anti-atherosclerotic or anti-restenotic drug induced by thrombin.