Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, reduces plasma eicosanoid levels and ameliorates endothelial dysfunction in diabetic mice 28 12

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Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, reduces plasma eicosanoid levels and ameliorates endothelial dysfunction in diabetic mice 12

Persistent ID (NDL): info:ndljp/pid/11977359

Material type: 博士論文

Author: Suto, Kumikoほか

Publisher: Japan Atherosclerosis Society

Publication date: 2021-12-01

Material Format: Digital

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Name of awarding university/degree: 徳島大学,博士（医学）

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Note (General)：: Aims: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in v...

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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
Volume: 28 12
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
Degree grantor/type: 徳島大学
Date Granted: 2021-03-23
Date Granted (W3CDTF): 2021-03-23
Dissertation Number: 甲第3505号
Degree Type: 博士（医学）
Conferring No. (Dissertation): 甲第3505号
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.
DOI: info:doi/10.5551/jat.61101
https://doi.org/info:doi/10.5551/jat.61101
Persistent ID (NDL): info:ndljp/pid/11977359
https://dl.ndl.go.jp/pid/11977359
Collection: 障害者向け資料
Collection (Materials For Handicapped People:1): テキストデータ
Collection (particular): 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
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2022-01-10T16:22:37+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
Availability of remote photoduplication service: 可
Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/116054
Data Provider (Database): 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