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ID 116054
Title Alternative
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
Author
Shinohara, Masakazu Kobe University
Ganbaatar, Byambasuren Tokushima University
Hirata, Ken-ichi Kobe University
Keywords
Pemafibrate
Eicosanoid
Diabetes
Endothelial function
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Atherosclerosis and Thrombosis
ISSN
13403478
18803873
Publisher
Japan Atherosclerosis Society
Volume
28
Issue
12
Start Page
1349
End Page
1360
Published Date
2021-12-01
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Kumiko Sutoの学位論文として提出され,学位審査・授与の対象となっている。
Rights
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/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3505号
Diploma Number
甲医第1494号
Granted Date
2021-03-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital