Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, reduces plasma eicosanoid levels and ameliorates endothelial dysfunction in diabetic mice

• Material Type: 博士論文
• Title: Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, reduces plasma eicosanoid levels and ameliorates endothelial dysfunction in diabetic mice
• Author/Editor: Suto, Kumiko; Fukuda, Daiju; Shinohara, Masakazu; Ganbaatar, Byambasuren; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Hirata, Ken-ichi; Sata, Masataka
• Author Heading: Suto, Kumiko; Fukuda, Daiju; Shinohara, Masakazu; Ganbaatar, Byambasuren; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Hirata, Ken-ichi; Sata, Masataka
• Publication, Distribution, etc.: Japan Atherosclerosis Society
• Publication Date: 2021-12-01
• Publication Date (W3CDTF): 2021-12-01
• Alternative Title: 新規選択的ペルオキシソーム増殖剤活性化受容体αモジュレーターであるペマフィブラートは血漿エイコサノイドを減少させ、糖尿病マウスの血管内皮機能障害を改善する; Effect of Pemafibrate on Eicosanoids
• Periodical title: Journal of Atherosclerosis and Thrombosis
• No. or year of volume/issue: 28 12
• Volume: 28
• Issue: 12
• Pages: 1349-1360
• ISSN (Periodical Title): ISSN : 1340-3478; ISSN : 1880-3873
• Degree grantor/type: 徳島大学
• Date Granted: 2021-03-23
• Dissertation Number: 甲第3505号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Pemafibrate; Eicosanoid; Diabetes; Endothelial function
• Target Audience: 一般
• Note (General): Aims: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, on plasma eicosanoid levels and endothelial function in diabetic mice. Methods: Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed. Results: Pemafibrate reduced both triglyceride and non-high-density lipoprotein-cholesterol levels (P＜0.01), without affecting body weight. It also decreased circulating levels of AA (P＜0.001), thromboxane B2 (P＜0.001), prostaglandin E2, leukotriene B4 (P＜0.05), and 5 hydroxyeicosatetraenoic acid (P＜0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-Δ12,14-prostaglandin J2, which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations (P＜0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it (P＜0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function. Conclusion: Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution license.( https://creativecommons.org/licenses/by-nc-sa/4.0/ )
• Related Material (DOI): 10.5551/jat.61101
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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