徳島大学 教育・研究者情報データベース(EDB)

1. (英) Aini K / (日) AINI KUNDUZIAYI / (読) あいに くんどうずあい

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2. 福田 大受

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3. (英) Tanaka K

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4. (英) Higashikuni Y

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5. (英) Hirata Yukina / (日) 平田 有紀奈 / (読) ひらた ゆきな

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6. 八木 秀介([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.地域・家庭医療学])

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7. 楠瀬 賢也

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8. 山田 博胤([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域循環器内科学])

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9. 添木 武([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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10. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

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(英) Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice

(英) Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE) mice. Eight-week-old nondiabetic ApoE mice fed a Western-type diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.

1. (英) Animals
2. (英) Apolipoproteins E
3. (英) Atherosclerosis
4. (英) Cell Culture Techniques
5. (英) Dipeptidyl-Peptidase IV Inhibitors
6. (英) Disease Models, Animal
7. (英) Endothelial Cells
8. (英) Endothelium, Vascular
9. (英) Mice
10. (英) Mice, Inbred C57BL
11. (英) Vascular Cell Adhesion Molecule-1
12. (英) Vildagliptin

1. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

1. (英) Article.ELocationID: 10.1536/ihj.19-117

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: Atherosclerosis

4. (英) KeywordList.Keyword: Diabetes mellitus

5. (英) KeywordList.Keyword: Endothelial function

6. (英) KeywordList.Keyword: GLP-1