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Eicosanoids and Aortic Aneurysm

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Bioactive Lipid Mediators

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Abstract

Some of the derivatives of arachidonic acid, namely, the 5-lipoxygenase (5-LO) metabolites leukotriene B4 (LTB4) and cysteinyl-leukotrienes (CysLTs) as well as the microsomal prostaglandin E2 synthase-1 (mPGES-1) product prostaglandin E2 (PGE2), can act as potent pro-inflammatory mediators in vascular diseases. Abdominal aortic aneurysm (AAA) is a vascular pathology characterized by the infiltration of the media and adventitia by immune cells and the subsequent degradation of the medial elastic lamina layer. In human AAA, cyclooxygenase-2 (COX-2) and 5-LO are abundantly expressed, and the roles of PGE2 and LTs in AAA have recently been a subject of intense investigation. In particular, the PGE2 receptor EP4 has been suggested to promote cytokine production and proteolytic activation, and the inhibition of EP4 signaling attenuates the progression of murine models of AAA. The LTs LTB4 and LTD4 have been shown to stimulate the release of a variety of cytokines and other mediators that can enhance degradation of the extracellular matrix, such as macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Pharmacological inhibition of these eicosanoids attenuate murine models of AAA. Because no pharmacological therapies are currently available for inhibiting the progression of AAA, regulation of the PGE2 and 5-LO pathways may serve as a new therapeutic strategy for AAA.

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Acknowledgments

This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (U.Y. and Y.I.), a Grant-in-Aid for Scientific Research on Innovative Areas (U.Y.: 1123116514; YI, 22136009), the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Ministry of Education, Culture, Sports, Science and Technology (U.Y.), the Yokohama Foundation for Advanced Medical Science (U.Y.), the Vehicle Racing Commemorative Foundation (U.Y.), and the Takeda Science Foundation (U.Y. and Y.I.).

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Authors and Affiliations

  1. Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura Kanazawaku, Yokohama, 236-0004, Japan

    Utako Yokoyama, Ryo Ishiwata & Yoshihiro Ishikawa

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  1. Utako Yokoyama
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  2. Ryo Ishiwata
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  3. Yoshihiro Ishikawa
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Correspondence to Utako Yokoyama .

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Editors and Affiliations

  1. Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takehiko Yokomizo

  2. Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Makoto Murakami

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Yokoyama, U., Ishiwata, R., Ishikawa, Y. (2015). Eicosanoids and Aortic Aneurysm. In: Yokomizo, T., Murakami, M. (eds) Bioactive Lipid Mediators. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55669-5_19

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