Regression of abdominal aortic aneurysms by pharmacological inhibition of c-Jun N-terminal kinase

Creators Yoshimura Koichi

Creators Aoki Hiroki

Creators Ikeda Yasuhiro

Creators Furutani Akira

Creators Hamano Kimikazu

Creators Matsuzaki Masunori

Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation and proteolytic degradation of the extracellular matrix (ECM). Recently, we identified c-Jun N-terminal kinase (JNK) as a key molecule in the pathogenesis of AAA. Human AAA tissue showed a high level of active JNK. In in vitro studies, JNK not only activated the expression of ECM-degrading enzymes, but also suppressed the expression of enzymes for ECM biosynthesis. Finally, pharmacological inhibition of JNK not only prevented the development of AAA but also caused the regression of established AAA in mouse models. Thus, pharmacological inhibition of JNK may provide a novel therapeutic option for treatment of human AAA.

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