ID | 63796 |
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Author |
Amioka, Naofumi
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Miyoshi, Toru
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
ORCID
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Yonezawa, Tomoko
Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Kondo, Megumi
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Akagi, Satoshi
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
ORCID
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Yoshida, Masashi
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Saito, Yukihiro
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nakamura, Kazufumi
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Ito, Hiroshi
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Abstract | Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture.
Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells. |
Keywords | pemafibrate
angiotensin II
abdominal aortic aneurysm
oxidative stress
catalase
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Published Date | 2022-06-30
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Publication Title |
Frontiers In Cardiovascular Medicine
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Volume | volume9
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Publisher | Frontiers Media SA
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Start Page | 904215
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ISSN | 2297-055X
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2022 Amioka, Miyoshi, Yonezawa, Kondo, Akagi, Yoshida, Saito, Nakamura and Ito.
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File Version | publisher
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DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.3389/fcvm.2022.904215
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License | https://creativecommons.org/licenses/by/4.0/
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Citation | Amioka N, Miyoshi T, Yonezawa T, Kondo M, Akagi S, Yoshida M, Saito Y, Nakamura K and Ito H (2022) Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms. Front. Cardiovasc. Med. 9:904215. doi: 10.3389/fcvm.2022.904215
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 18K08758
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