Regulation of Vascular Smooth Muscle Cell Proliferation by Nuclear Factor-κB and Its Inhibitor, I-κB

Proliferation of vascular smooth muscle cells (SMC) is a crucial event in the formation of atherosclerotic tissues and is regulated by nuclear transcriptional factors including nuclear factor-κB (NF-κB). We constructed a reporter gene assay to measure NF-κB-dependent transcriptional activity in SMC. Thrombin receptor-activating peptide (TRAP) and basic fibroblast growth factor (bFGF) stimulated SMC proliferation and rapidly enhanced the NF-κB transcriptional activity in a dose-dependent manner. 4-Cyano-5,5-bis-(methoxyphenyl)4-pentenoic acid (E5510) significantly inhibited SMC proliferation and also suppressed NF-κB transcription stimulated by TRAP and bFGF. In contrast, although tumor necrosis factor (TNF)-α activated NF-κB transcription, E5510 had no effect on TNF-α-induced activation. NF-κB was activated after the stimulation of TRAP, bFGF, and TNF-α in electrophoretic mobility shift assay, and E5510 suppressed the NF-κB activation induced by TRAP and the activation by of and of was in NF-κB activation after the stimulation of TRAP and bFGF. of suppressed NF-κB transcriptional activity and SMC of was rapidly induced by TRAP and by TRAP and induced and NF-κB activation a TNF-α and in NF-κB activation induced by TRAP and bFGF. Proliferation of vascular smooth muscle cells (SMC) is a crucial event in the formation of atherosclerotic tissues and is regulated by nuclear transcriptional factors including nuclear factor-κB (NF-κB). We constructed a reporter gene assay to measure NF-κB-dependent transcriptional activity in SMC. Thrombin receptor-activating peptide (TRAP) and basic fibroblast growth factor (bFGF) stimulated SMC proliferation and rapidly enhanced the NF-κB transcriptional activity in a dose-dependent manner. 4-Cyano-5,5-bis-(methoxyphenyl)4-pentenoic acid (E5510) significantly inhibited SMC proliferation and also suppressed NF-κB transcription stimulated by TRAP and bFGF. In contrast, although tumor necrosis factor (TNF)-α activated NF-κB transcription, E5510 had no effect on TNF-α-induced activation. NF-κB was activated after the stimulation of TRAP, bFGF, and TNF-α in electrophoretic mobility shift assay, and E5510 suppressed the NF-κB activation induced by TRAP and the activation by of and of was in NF-κB activation after the stimulation of TRAP and bFGF. of suppressed NF-κB transcriptional activity and SMC of was rapidly induced by TRAP and by TRAP and induced and NF-κB activation a TNF-α and in NF-κB activation induced by TRAP and bFGF. nuclear factor-κB smooth muscle cells peptide basic fibroblast growth factor tumor necrosis factor acid electrophoretic mobility shift assay cells to a in gene and proliferation NF-κB the of and atherosclerotic tissues NF-κB of NF-κB is enhanced in vascular SMC proliferation after In NF-κB is activated by growth and in SMC of of NF-κB inhibited SMC proliferation and of in the NF-κB is in SMC proliferation in and in Proliferation of SMC in the formation of in and vascular after and to NF-κB activation in SMC proliferation is is of and is and by and by a NF-κB is is and to after in vascular of NF-κB activation and SMC proliferation of atherosclerotic the of of of NF-κB was activated in SMC of atherosclerotic in vascular tissues a to the activation of NF-κB in SMC proliferation on vascular of vascular SMC regulated by growth factors and in the formation of atherosclerotic of factors to SMC proliferation basic fibroblast growth factor and tumor necrosis of is by receptor-activating peptide factors to NF-κB activation in the a acid (E5510) suppressed NF-κB activation induced by in SMC In on NF-κB activation and to regulated by bFGF, TRAP, and We in TRAP and induced and NF-κB activation and TNF-α is activated in SMC proliferation in and a in NF-κB activation in also the of in NF-κB activation induced by TRAP and by of vascular SMC regulated by growth factors and in the formation of atherosclerotic of factors to SMC proliferation bFGF, and of is by transcriptional factors NF-κB SMC We the effect of growth factors and TNF-α on in SMC by TRAP and induced SMC in a dose-dependent TRAP and the activity to and to the TNF-α the activity to E5510 inhibited SMC proliferation in in vascular the effect of E5510 on SMC E5510 inhibited induced by TRAP and E5510 the activity of TRAP to the E5510 the activity of in a dose-dependent and the was and E5510 had no effect on and the effect of E5510 on the in TRAP and in a manner. TRAP and TNF-α induced the in no and E5510 suppressed the in induced by TRAP and bFGF. E5510 the activity of TRAP and the activity of to the E5510 had no effect on of and cells TRAP and SMC TNF-α was and E5510 inhibited and proliferation of SMC after the stimulation of TRAP and of TRAP and on SMC SMC TRAP, bFGF, and TNF-α and and was cells E5510 and TRAP and TNF-α to in SMC of and in vascular and was induced SMC proliferation measure the NF-κB-dependent transcriptional SMC NF-κB in the of and NF-κB transcription of gene TRAP, bFGF, and TNF-α stimulated the transcriptional activity in a dose-dependent TRAP enhanced the activity significantly and and TNF-α the transcriptional activity and E5510 suppressed the activity stimulated by TRAP and In contrast, E5510 the TNF-α-induced transcriptional activity the NF-κB-dependent transcriptional activity was induced by TRAP and a of TNF-α in of TRAP and on NF-κB-dependent transcriptional SMC NF-κB-dependent TRAP, bFGF, and TNF-α activity was and and was cells E5510 and TRAP TNF-α activation of by NF-κB to NF-κB activity to to after SMC the nuclear in NF-κB the to and the TRAP, bFGF, and NF-κB activation in to was was in the NF-κB transcriptional activity in the reporter gene E5510 was to the the suppressed the NF-κB activation in the stimulation by TRAP and bFGF. In contrast, E5510 the had no effect on the activation by assay was and and and induced the shift of the and induced the shift of the of the the of the of NF-κB NF-κB and and in of the the of NF-κB activity in of E5510 on NF-κB activity in SMC E5510 and TRAP and TNF-α the cells in NF-κB by a nuclear to in the of the the nuclear in and E5510 had no effect on activity in the of TRAP, bFGF, and TNF-α of NF-κB activity in was in and the of activity E5510 suppressed the NF-κB activation induced by TRAP by and the activation by by In contrast, E5510 the had no effect on the activation by E5510 the activity of E5510 suppressed NF-κB activity induced by TRAP and the activity by TNF-α and the effect was to NF-κB to of NF-κB activity activity by E5510 in NF-κB activity and activity and a to the the of activity is regulated by and the of in NF-κB activation. SMC TRAP, bFGF, and and the of and was by was after stimulation by TRAP and bFGF. the of the was In contrast, TNF-α the in SMC. the the of was and after stimulation by of TRAP, bFGF, and TNF-α and after and was regulated in a in SMC and a in NF-κB activation induced by TRAP and of and after stimulation of TRAP and SMC TRAP and TNF-α and in by the E5510 suppressed NF-κB the of E5510 on the of and by cells the suppressed of in the activation by TRAP and bFGF. E5510 had no effect on induced by the E5510 suppressed in the activation by and E5510 had no effect on induced by E5510 was to the of of was in NF-κB activation after the stimulation of TRAP and in of and by E5510 and TRAP and TNF-α and in by is a in the a in SMC and activity is induced SMC proliferation in in the the regulated NF-κB activity in SMC NF-κB reporter gene assay and significantly the NF-κB transcriptional activity induced by TRAP and bFGF. the NF-κB transcriptional activity of TRAP and was to the the had no effect on In the effect of on SMC proliferation was in assay suppressed SMC proliferation induced by TRAP and bFGF. the proliferation induced by TRAP and to and of the was in NF-κB activation and SMC of NF-κB activity and growth activity by and and TRAP NF-κB-dependent activity was by assay and activity was by and was the effect of E5510 on activity in SMC was assay TRAP and stimulated activation. TRAP significantly activated and after the and the activity was to the of cells induced the activation and the activity rapidly and In contrast, TNF-α had no effect on activity of although TNF-α activated the effect of E5510 on was E5510 the activity stimulated by TRAP and bFGF. was in NF-κB activation and SMC proliferation induced by TRAP and bFGF, E5510 suppressed a in the of activation to NF-κB activation in SMC of TRAP and E5510 on activity in SMC. SMC TRAP and TNF-α activity was and cells in the of E5510 and TRAP and TNF-α activity was of of vascular SMC is a crucial event in the formation of atherosclerotic tissues and is regulated by growth We the of growth factors on SMC TRAP and bFGF, stimulated proliferation in assay and E5510 inhibited SMC proliferation induced by TRAP and bFGF. In E5510 inhibited SMC proliferation in in and E5510 is a of SMC proliferation in and in and activated the NF-κB-dependent transcription in SMC. E5510 suppressed NF-κB activation of TRAP and and also and of the effect of E5510 on NF-κB activation was to the of We the of NF-κB activation and SMC to NF-κB activation. TRAP and and NF-κB activation. TNF-α a E5510 inhibited the of and E5510 was In of and E5510 had a effect on and of effect was to on the of of and by E5510 in and a activity of NF-κB activation and factor in cells TNF-α-induced NF-κB and no effect on the in the induced in SMC and cells by growth factors and and SMC proliferation a the of activity SMC proliferation is to NF-κB activity in SMC the effect of E5510 on activity to the of and NF-κB the E5510 is a of and SMC proliferation of by E5510 in In the E5510 the activity of and and and in of and SMC proliferation of and the activation of NF-κB activation in cells and cells NF-κB-dependent factor gene is inhibited by and by of of nuclear of NF-κB the of and the of the transcriptional NF-κB activity to the activation of activation in SMC is suppressed by also activity in SMC in to E5510 activation by TRAP and bFGF. E5510 NF-κB activation in a is in E5510 suppressed the and NF-κB activation by TRAP and the activation by TNF-α in SMC. the and NF-κB activation by TRAP and is a a of to NF-κB activation the of a inhibited and NF-κB activation induced by and acid the activation by and factor in cells is NF-κB and inhibited the of factor and induced by and the induced by TNF-α to NF-κB activation in the by and to NF-κB activation and in activation proliferation of cells SMC in NF-κB activation is induced a Thrombin and NF-κB in of and in cells NF-κB activation the of NF-κB activation in SMC. E5510 suppressed the of in the of a E5510 the the of was in NF-κB activation SMC proliferation after the stimulation of TRAP and bFGF. cells the suppressed of in the activation by TRAP and bFGF, E5510 had no effect on induced by the E5510 suppressed in the activation by and TNF-α effect on induced by and NF-κB activation the of by is and by and and of the of and of the activity of activation of is stimulated by the of of SMC and proliferation and to is the of is a of the of E5510 to and NF-κB activation to TRAP and bFGF, TNF-α was a SMC proliferation in although TNF-α was to NF-κB in SMC. is TNF-α to and TNF-α the of and SMC proliferation NF-κB activation to In the proliferation is induced by by TRAP, although NF-κB activation In the of TNF-α SMC proliferation in is activated by the of TNF-α and transcriptional factors NF-κB and NF-κB is induced by TNF-α and by Thrombin and TNF-α activated NF-κB in Thrombin and TRAP TNF-α-induced in proliferation in to NF-κB TRAP and and NF-κB activation a and in NF-κB activation to SMC the of SMC proliferation is the to vascular E5510 is a and a to NF-κB-dependent SMC to a in gene and proliferation NF-κB the of and atherosclerotic tissues NF-κB of NF-κB is enhanced in vascular SMC proliferation after In NF-κB is activated by growth and in SMC of of NF-κB inhibited SMC proliferation and of in the NF-κB is in SMC proliferation in and in Proliferation of SMC in the formation of in and vascular after and to NF-κB activation in SMC proliferation is is of and is and by and by a NF-κB is is and to after in vascular of NF-κB activation and SMC proliferation of atherosclerotic the of of of NF-κB was activated in SMC of atherosclerotic in vascular tissues a to the activation of NF-κB in SMC proliferation on vascular Proliferation of vascular SMC regulated by growth factors and in the formation of atherosclerotic of factors to SMC proliferation basic fibroblast growth factor and tumor necrosis of is by receptor-activating peptide factors to NF-κB activation in the a acid (E5510) suppressed NF-κB activation induced by in SMC In on NF-κB activation and to regulated by bFGF, TRAP, and We in TRAP and induced and NF-κB activation and TNF-α is activated in SMC proliferation in and a in NF-κB activation in also the of in NF-κB activation induced by TRAP and by of vascular SMC regulated by growth factors and in the formation of atherosclerotic of factors to SMC proliferation bFGF, and of is by transcriptional factors NF-κB SMC We the effect of growth factors and TNF-α on in SMC by TRAP and induced SMC in a dose-dependent TRAP and the activity to and to the TNF-α the activity to E5510 inhibited SMC proliferation in in vascular the effect of E5510 on SMC E5510 inhibited induced by TRAP and E5510 the activity of TRAP to the E5510 the activity of in a dose-dependent and the was and E5510 had no effect on and the effect of E5510 on the in TRAP and in a manner. TRAP and TNF-α induced the in no and E5510 suppressed the in induced by TRAP and bFGF. E5510 the activity of TRAP and the activity of to the E5510 had no effect on of and cells TRAP and SMC TNF-α was and E5510 inhibited and proliferation of SMC after the stimulation of TRAP and to in SMC of and in vascular and was induced SMC proliferation measure the NF-κB-dependent transcriptional SMC NF-κB in the of and NF-κB transcription of gene TRAP, bFGF, and TNF-α stimulated the transcriptional activity in a dose-dependent TRAP enhanced the activity significantly and and TNF-α the transcriptional activity and E5510 suppressed the activity stimulated by TRAP and In contrast, E5510 the TNF-α-induced transcriptional activity the NF-κB-dependent transcriptional activity was induced by TRAP and a of TNF-α in of TRAP and on NF-κB-dependent transcriptional SMC NF-κB-dependent TRAP, bFGF, and TNF-α activity was and and was cells E5510 and TRAP TNF-α activation of by NF-κB to NF-κB activity to to after SMC the nuclear in NF-κB the to and the TRAP, bFGF, and NF-κB activation in to was was in the NF-κB transcriptional activity in the reporter gene E5510 was to the the suppressed the NF-κB activation in the stimulation by TRAP and bFGF. In contrast, E5510 the had no effect on the activation by assay was and and and induced the shift of the and induced the shift of the of the the of the of NF-κB NF-κB and and in of the the of NF-κB activity in of E5510 on NF-κB activity in SMC E5510 and TRAP and TNF-α the cells in NF-κB by a nuclear to in the of the the nuclear in and E5510 had no effect on activity in the of TRAP, bFGF, and TNF-α of NF-κB activity in was in and the of activity E5510 suppressed the NF-κB activation induced by TRAP by and the activation by by In contrast, E5510 the had no effect on the activation by E5510 the activity of E5510 suppressed NF-κB activity induced by TRAP and the activity by TNF-α and the effect was to NF-κB to of NF-κB activity activity by E5510 in NF-κB activity and activity and a to the the of activity is regulated by and the of in NF-κB activation. SMC TRAP, bFGF, and and the of and was by was after stimulation by TRAP and bFGF. the of the was In contrast, TNF-α the in SMC. the the of was and after stimulation by of TRAP, bFGF, and TNF-α and after and was regulated in a in SMC and a in NF-κB activation induced by TRAP and of and after stimulation of TRAP and SMC TRAP and TNF-α and in by the E5510 suppressed NF-κB the of E5510 on the of and by cells the suppressed of in the activation by TRAP and bFGF. E5510 had no effect on induced by the E5510 suppressed in the activation by and E5510 had no effect on induced by E5510 was to the of of was in NF-κB activation after the stimulation of TRAP and in of and by E5510 and TRAP and TNF-α and in by is a in the a in SMC and activity is induced SMC proliferation in in the the regulated NF-κB activity in SMC NF-κB reporter gene assay and significantly the NF-κB transcriptional activity induced by TRAP and bFGF. the NF-κB transcriptional activity of TRAP and was to the the had no effect on In the effect of on SMC proliferation was in assay suppressed SMC proliferation induced by TRAP and bFGF. the proliferation induced by TRAP and to and of the was in NF-κB activation and SMC of NF-κB activity and growth activity by and and TRAP NF-κB-dependent activity was by assay and activity was by and was the effect of E5510 on activity in SMC was assay TRAP and stimulated activation. TRAP significantly activated and after the and the activity was to the of cells induced the activation and the activity rapidly and In contrast, TNF-α had no effect on activity of although TNF-α activated the effect of E5510 on was E5510 the activity stimulated by TRAP and bFGF. was in NF-κB activation and SMC proliferation induced by TRAP and bFGF, E5510 suppressed a in the of activation to NF-κB activation in SMC of TRAP and E5510 on activity in SMC. SMC TRAP and TNF-α activity was and cells in the of E5510 and TRAP and TNF-α activity was of Proliferation of vascular SMC regulated by growth factors and in the formation of atherosclerotic of factors to SMC proliferation bFGF, and of is by transcriptional factors NF-κB SMC We the effect of growth factors and TNF-α on in SMC by TRAP and induced SMC in a dose-dependent TRAP and the activity to and to the TNF-α the activity to E5510 inhibited SMC proliferation in in vascular the effect of E5510 on SMC E5510 inhibited induced by TRAP and E5510 the activity of TRAP to the E5510 the activity of in a dose-dependent and the was and E5510 had no effect on and the effect of E5510 on the in TRAP and in a manner. TRAP and TNF-α induced the in no and E5510 suppressed the in induced by TRAP and bFGF. E5510 the activity of TRAP and the activity of to the E5510 had no effect on of and cells TRAP and SMC TNF-α was and E5510 inhibited and proliferation of SMC after the stimulation of TRAP and bFGF. NF-κB to in SMC of and in vascular and was induced SMC proliferation measure the NF-κB-dependent transcriptional SMC NF-κB in the of and NF-κB transcription of gene TRAP, bFGF, and TNF-α stimulated the transcriptional activity in a dose-dependent TRAP enhanced the activity significantly and and TNF-α the transcriptional activity and E5510 suppressed the activity stimulated by TRAP and In contrast, E5510 the TNF-α-induced transcriptional activity the NF-κB-dependent transcriptional activity was induced by TRAP and a of TNF-α in SMC. activation of by NF-κB to NF-κB activity to to after SMC the nuclear in NF-κB the to and the TRAP, bFGF, and NF-κB activation in to was was in the NF-κB transcriptional activity in the reporter gene E5510 was to the the suppressed the NF-κB activation in the stimulation by TRAP and bFGF. In contrast, E5510 the had no effect on the activation by assay was and and and induced the shift of the and induced the shift of the of the the of the of NF-κB NF-κB and and in of the the of NF-κB activity in SMC. We the nuclear in and E5510 had no effect on activity in the of TRAP, bFGF, and TNF-α of NF-κB activity in was in and the of activity E5510 suppressed the NF-κB activation induced by TRAP by and the activation by by In contrast, E5510 the had no effect on the activation by E5510 the activity of E5510 suppressed NF-κB activity induced by TRAP and the activity by TNF-α and the effect was to NF-κB to NF-κB activity is regulated by and the of in NF-κB activation. SMC TRAP, bFGF, and and the of and was by was after stimulation by TRAP and bFGF. the of the was In contrast, TNF-α the in SMC. the the of was and after stimulation by of TRAP, bFGF, and TNF-α and after and was regulated in a in SMC and a in NF-κB activation induced by TRAP and bFGF. the E5510 suppressed NF-κB the of E5510 on the of and by cells the suppressed of in the activation by TRAP and bFGF. E5510 had no effect on induced by the E5510 suppressed in the activation by and E5510 had no effect on induced by E5510 was to the of of was in NF-κB activation after the stimulation of TRAP and in SMC. is a in the a in SMC and activity is induced SMC proliferation in in the the regulated NF-κB activity in SMC NF-κB reporter gene assay and significantly the NF-κB transcriptional activity induced by TRAP and bFGF. the NF-κB transcriptional activity of TRAP and was to the the had no effect on In the effect of on SMC proliferation was in assay suppressed SMC proliferation induced by TRAP and bFGF. the proliferation induced by TRAP and to and of the was in NF-κB activation and SMC the effect of E5510 on activity in SMC was assay TRAP and stimulated activation. TRAP significantly activated and after the and the activity was to the of cells induced the activation and the activity rapidly and In contrast, TNF-α had no effect on activity of although TNF-α activated the effect of E5510 on was E5510 the activity stimulated by TRAP and bFGF. was in NF-κB activation and SMC proliferation induced by TRAP and bFGF, E5510 suppressed a in the of activation to NF-κB activation in SMC of vascular SMC is a crucial event in the formation of atherosclerotic tissues and is regulated by growth We the of growth factors on SMC TRAP and bFGF, stimulated proliferation in assay and E5510 inhibited SMC proliferation induced by TRAP and bFGF. In E5510 inhibited SMC proliferation in in and E5510 is a of SMC proliferation in and in and activated the NF-κB-dependent transcription in SMC. E5510 suppressed NF-κB activation of TRAP and and also and of the effect of E5510 on NF-κB activation was to the of We the of NF-κB activation and SMC E5510 inhibited the of and E5510 was In of and E5510 had a effect on and of effect was to on the of of and by E5510 in and a activity of NF-κB activation and factor in cells TNF-α-induced NF-κB and no effect on the in the induced in SMC and cells by growth factors and and SMC proliferation a the of activity SMC proliferation is to NF-κB activity in SMC the effect of E5510 on activity to the of and NF-κB the E5510 is a of and SMC proliferation of by E5510 in In the E5510 the activity of and and and in of and SMC proliferation of and the activation of NF-κB activation in cells and cells NF-κB-dependent factor gene is inhibited by and by of of nuclear of NF-κB the of and the of the transcriptional NF-κB activity to the activation of activation in SMC is suppressed by also activity in SMC in to E5510 activation by TRAP and bFGF. E5510 NF-κB activation in a is in E5510 suppressed the and NF-κB activation by TRAP and the activation by TNF-α in SMC. the and NF-κB activation by TRAP and is a a of to NF-κB activation the of a inhibited and NF-κB activation induced by and acid the activation by and factor in cells is NF-κB and inhibited the of factor and induced by and the induced by TNF-α to NF-κB activation in the by and to NF-κB activation and in activation proliferation of cells SMC in NF-κB activation is induced a Thrombin and NF-κB in of and in cells NF-κB activation the of NF-κB activation in SMC. E5510 suppressed the of in the of a E5510 the the of was in NF-κB activation SMC proliferation after the stimulation of TRAP and bFGF. cells the suppressed of in the activation by TRAP and bFGF, E5510 had no effect on induced by the E5510 suppressed in the activation by and TNF-α effect on induced by and NF-κB activation the of by is and by and and of the of and of the activity of activation of is stimulated by the of of SMC and proliferation and to is the of is a of the of E5510 to and NF-κB activation to TRAP and bFGF, TNF-α was a SMC proliferation in although TNF-α was to NF-κB in SMC. is TNF-α to and TNF-α the of and SMC proliferation NF-κB activation to In the proliferation is induced by by TRAP, although NF-κB activation In the of TNF-α SMC proliferation in is activated by the of TNF-α and transcriptional factors NF-κB and NF-κB is induced by TNF-α and by Thrombin and TNF-α activated NF-κB in Thrombin and TRAP TNF-α-induced in proliferation in to NF-κB TRAP and and NF-κB activation a and in NF-κB activation to SMC the of SMC proliferation is the to vascular E5510 is a and a to NF-κB-dependent SMC Proliferation of vascular SMC is a crucial event in the formation of atherosclerotic tissues and is regulated by growth We the of growth factors on SMC TRAP and bFGF, stimulated proliferation in assay and E5510 inhibited SMC proliferation induced by TRAP and bFGF. In E5510 inhibited SMC proliferation in in and E5510 is a of SMC proliferation in and in TRAP and activated the NF-κB-dependent transcription in SMC. E5510 suppressed NF-κB activation of TRAP and and also and of the effect of E5510 on NF-κB activation was to the of We the of NF-κB activation and SMC E5510 inhibited the of and E5510 was In of and E5510 had a effect on and of effect was to on the of of and by E5510 in and a activity of NF-κB activation and factor in cells TNF-α-induced NF-κB and no effect on the in the induced in SMC and cells by growth factors and and SMC proliferation a the of activity SMC proliferation is to NF-κB activity in SMC the effect of E5510 on activity to the of and NF-κB activation. the E5510 is a of and SMC proliferation of by E5510 in In the E5510 the activity of and and and in of and SMC proliferation of and the activation of NF-κB activation in cells and cells NF-κB-dependent factor gene is inhibited by and by of of nuclear of NF-κB the of and the of the transcriptional NF-κB activity to the activation of activation in SMC is suppressed by also activity in SMC in to E5510 activation by TRAP and bFGF. E5510 NF-κB activation in a manner. is in E5510 suppressed the and NF-κB activation by TRAP and the activation by TNF-α in SMC. the and NF-κB activation by TRAP and is a a of to NF-κB activation the of a inhibited and NF-κB activation induced by and acid the activation by and factor in cells is NF-κB and inhibited the of factor and induced by and the induced by TNF-α to NF-κB activation in the by and to NF-κB activation and in activation proliferation of cells SMC in NF-κB activation is induced a Thrombin and NF-κB in of and in cells NF-κB activation the of NF-κB activation in SMC. E5510 suppressed the of in the of a E5510 the the of was in NF-κB activation SMC proliferation after the stimulation of TRAP and bFGF. cells the suppressed of in the activation by TRAP and bFGF, E5510 had no effect on induced by the E5510 suppressed in the activation by and TNF-α effect on induced by and NF-κB activation the of by is and by and and of the of and of the activity of activation of is stimulated by the of of SMC and proliferation and to is the of is a of the of E5510 to and NF-κB activation In to TRAP and bFGF, TNF-α was a SMC proliferation in although TNF-α was to NF-κB in SMC. is TNF-α to and TNF-α the of and SMC proliferation NF-κB activation to In the proliferation is induced by by TRAP, although NF-κB activation In the of TNF-α SMC proliferation in is activated by the of TNF-α and transcriptional factors NF-κB and NF-κB is induced by TNF-α and by Thrombin and TNF-α activated NF-κB in Thrombin and TRAP TNF-α-induced in proliferation in to NF-κB activation. In TRAP and and NF-κB activation a and in NF-κB activation to SMC the of SMC proliferation is the to vascular E5510 is a and a to NF-κB-dependent SMC We