Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice

[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...

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Published in:Journal of Atherosclerosis and Thrombosis 2021, Vol.28 (12), p.1349-1360
Main Authors: Kumiko Suto, Daiju Fukuda, Masakazu Shinohara, Byambasuren Ganbaatar, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Ken-ichi Hirata, Masataka Sata
Format: Article
Language:Japanese
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Summary:[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
ISSN:1340-3478