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

• 資料種別: 博士論文
• ISSN: 1340-3478
• タイトル: Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, reduces plasma eicosanoid levels and ameliorates endothelial dysfunction in diabetic mice
• 巻次・部編番号: 28 12
• 著者・編者: Suto, Kumiko; Fukuda, Daiju; Shinohara, Masakazu; Ganbaatar, Byambasuren; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Hirata, Ken-ichi; Sata, Masataka
• 著者標目: Suto, Kumiko; Fukuda, Daiju; Shinohara, Masakazu; Ganbaatar, Byambasuren; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Hirata, Ken-ichi; Sata, Masataka
• 出版事項: Japan Atherosclerosis Society
• 出版年月日等: 2021-12-01
• 出版年（W3CDTF）: 2021-12-01
• 並列タイトル等: 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
• タイトル（掲載誌）: Journal of Atherosclerosis and Thrombosis
• 授与機関名: 徳島大学
• 授与年月日: 2021-03-23
• 授与年月日（W3CDTF）: 2021-03-23
• 報告番号: 甲第3505号
• 学位: 博士（医学）
• 博論授与番号: 甲第3505号
• 本文の言語コード: eng
• 件名標目: Pemafibrate; Eicosanoid; Diabetes; Endothelial function
• 対象利用者: 一般
• 一般注記: 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.
• DOI: info:doi/10.5551/jat.61101; https://doi.org/info:doi/10.5551/jat.61101
• 国立国会図書館永続的識別子: info:ndljp/pid/11977359; https://dl.ndl.go.jp/pid/11977359
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2022-01-10T16:22:37+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/116054
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp