Activation of NF kappa B is essential but not sufficient to stimulate mitogenesis of vascular smooth muscle cells

This study investigates the role of the transcription factor NF kappa B in thrombin- and thrombin receptor activating peptide (TRAP, SFLLRNPNDKYEPYF)-induced mitogenesis of cultured bovine coronary artery smooth muscle cells (SMC). Stimulation of resting cells by thrombin (10 nM) or TRAP (10-100 mu M) resulted in a comparable time-dependent activation of NF kappa B as detected by Western blotting and electrophoretic mobility shift assay (EMSA) of nuclear extracts. The NF kappa B activation was antagonized by N-acetyl-L-cysteine (20 mM) and pentoxifylline (0.5 mM). Thrombin caused a 3-4-fold increase in [H-3]thymidine incorporation within 24 h which was prevented by inhibitors of NF kappa B activation. In contrast, TRAP did not cause any mitogenic response. These results demonstrate that activation of NF kappa B is an essential but not a sufficient signal for SMC mitogenesis. (C) 1997 Academic Press.