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Turning back the clock: regression of abdominal aortic aneurysms via pharmacotherapy

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Abstract

Abdominal aortic aneurysm (AAA) is a common disease that causes progressive expansion and rupture of the aorta with high mortality. There is a large and unmet need for nonsurgical treatment for AAA. Research has shown that an intricate network of inflammatory cells and interstitial cells contributes to the formation of AAA by producing pro-inflammatory mediators that activate enzymes to degrade the extracellular matrix (ECM) and impair ECM biosynthesis. Pharmacological agents such as statins and angiotensin-converting enzyme inhibitors may promote tissue stabilization in AAA by diminishing pro-inflammatory signaling and normalizing metabolism of the ECM. Our recent experiments in animal models demonstrate that inhibition of c-Jun N terminal kinase (JNK) inhibits multiple pathological processes and causes regression of established AAA. Thus, emerging evidence indicates that pharmacological intervention targeting pro-inflammatory signaling and abnormal ECM metabolism is a promising strategy for treatment of AAA.

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Acknowledgments

We would like to thank our collaborators. We regret that many excellent studies related to this topic could not be mentioned because of space limitations. This work was supported by: Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science (HA, KY, and MM), Japan Heart Foundation/Zeria Pharmaceutical Grant for Research on Cardiovascular Disease (HA), a New Frontier Project from Yamaguchi University (HA and KY), a grant from the Takeda Science Foundation (HA), and a grant from the Sankyo Company to the Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine.

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  1. Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Hiroki Aoki, Koichi Yoshimura & Masunori Matsuzaki

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  1. Hiroki Aoki
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  2. Koichi Yoshimura
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  3. Masunori Matsuzaki
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Correspondence to Hiroki Aoki.

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Aoki, H., Yoshimura, K. & Matsuzaki, M. Turning back the clock: regression of abdominal aortic aneurysms via pharmacotherapy. J Mol Med 85, 1077–1088 (2007). https://doi.org/10.1007/s00109-007-0213-2

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  • DOI: https://doi.org/10.1007/s00109-007-0213-2

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