Involvement of NF-kappa B activation in thrombin-induced human vascular smooth muscle cell proliferation.

A thrombin receptor has been cloned and is thought to mediate a variety of thrombin-induced responses. However, the transcription factors important for postreceptor signaling have been little clarified. The post-receptor signals are mediated by several protein kinases responsible for NF-kappa B activation, and most thrombin-inducible genes have the kappa B sequence in the regulatory elements. The possibility that NF-kappa B may participate in thrombin signaling was therefore investigated in cultured human vascular smooth muscle cells (VSMCs). Thrombin receptor stimulation resulted in activation of NF-kappa B. Furthermore, treatment of cells with antisense p65 ODNs of NF-kappa B inhibited thrombin-stimulated growth of VSMC in vitro. Results indicate that the activation of NF-kappa B is involved in thrombin signaling and that this pathway causes the proliferation of VSMC induced by thrombin. Therapeutic potential of antisense NF-kappa B ODNs for the treatment with atherosclerosis and restenosis is also indicated.