JNK and c-Jun but not ERK and c-Fos are associated with sustained neointima-formation after balloon injury

Background Formation of neointima after balloon angioplasty is regulated vi a inducible transcription factors (ITF), such as c-Jun and c-Fos, depending on mitogen activated protein (MAP) kinases, which have been shown to be ac tivated after balloon injury. The precise localization of activated MAP-kin ases and concomitant expression of transcription factors in the vessel wall remains to be elucidated. We have now studied the localization and time-de pendent expression of MAP-kinases together with corresponding ITFs in the r at carotid angioplasty model. Design Animals were sacrificed at 0.5, 6 and 24 h and 3, 5, 7, 14 and 28 da ys after injury. Cryocut sections were stained using antibodies directed ag ainst c-Jun, phosphorylated c-Jun, c-Fos, c-Jun amino-terminal kinase (JNK) , extracellular signal related kinase (ERK), von Willebrand factor, ki67 an tigen, and alpha-actin. Results c-Jun expression was strongly induced in smooth muscle cells (SMC) 30 min after injury and remained upregulated for 24 h, thereafter dropping to basal levels at day 3. Re-expression was observed at day 7 and 14 but no t day 28. Expression patterns of JNK and phosphorylated c-Jun were highly c ongruent to that of c-Jun. In contrast, c-Fos expression was restricted to 30 min and, less pronounced than c-Jun and JNK, was visible after 7 days. A lso, its expression was congruent with the presence of ERK. Conclusions These findings demonstrate a clear association between MAP-kina ses and their transcription factor substrates in vivo with a predominant as sociation of JNK and c-Jun with sustained SMC proliferation.