Increased expression of phosphorylated c-Jun amino-terminal kinase and phosphorylated c-Jun in human cerebral aneurysms: role of the c-Jun amino-terminal kinase/c-Jun pathway in apoptosis of vascular walls.

Abstract

Vascular remodeling via apoptotic mechanisms is an important factor in vascular diseases. c-Jun amino-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and initiates apoptosis mainly via phosphorylation of the c-Jun transcription factor. We performed this study to clarify the roles of the JNK/c-Jun pathway and apoptosis in the pathogenesis of cerebral aneurysms. Cerebral aneurysms from 12 patients and control vessels from 5 patients were studied. We analyzed the expression of phosphorylated JNK and phosphorylated c-Jun in cerebral aneurysms by using immunohistochemical methods. Immunoreactivity for phosphorylated JNK and phosphorylated c-Jun was increased in the vascular walls of the cerebral aneurysms studied. Immunoreactivity for single-stranded deoxyribonucleic acid (a marker of deoxyribonucleic acid damage) was also increased in aneurysmal tissue, compared with control vessels, and was colocalized with that for phosphorylated JNK and phosphorylated c-Jun in smooth muscle cells. These observations may lead to better understanding of the role of the JNK/c-Jun pathway in the development of cerebral aneurysms and to new strategies for treatment.