Curcumin attenuates rat thoracic aortic aneurysm formation by inhibition of the c-Jun N-terminal kinase pathway and apoptosis.

ABSTRACT

OBJECTIVE: Recent studies have suggested that c-Jun N-terminal kinase (JNK) plays an important role in the formation of abdominal aortic aneurysms, and that direct blockade of JNK by specific inhibitors can effectively prevent the progression of aortic aneurysms. A study has demonstrated that curcumin can suppress the development of experimental abdominal aortic aneurysms by inhibiting inflammation. We sought to investigate whether curcumin could inhibit JNK pathways and apoptosis in thoracic aortic aneurysms. METHODS: We used a rat model of a CaCl2-induced thoracic aortic aneurysm followed by daily oral gavage with curcumin 100 mg/kg or vehicle alone. After treatment for 4 wk, tissue specimens were obtained for histologic assessments, and tissue composition was evaluated using immunohistochemistry, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. RESULTS: Curcumin significantly suppressed the CaCl2-induced expansion of the thoracic aortic diameter and the structural preservation of medial elastin fibers. Most importantly, curcumin treatment significantly inhibited the phosphorylation of JNK and c-Jun, accompanied by less cell apoptosis in thoracic aortic aneurysm tissues. Furthermore, the expression levels of caspase-3 and the Bax/Bcl-2 ratio were significantly decreased in the aortic walls of curcumin-treated rats. CONCLUSION: The present study indicates that the beneficial effect of curcumin on degenerative aortic aneurysms is related to the inhibition of JNK and apoptosis in the walls of thoracic aortic aneurysms.