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

• Material Type: 博士論文
• Title: Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice
• Author/Editor: Aini, Kunduziayi; Fukuda, Daiju; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Sata, Masataka
• Author Heading: Aini, Kunduziayi; Fukuda, Daiju; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Sata, Masataka
• Publication, Distribution, etc.: International Heart Journal Association
• Publication Date: 2019-11-30
• Publication Date (W3CDTF): 2019-11-30
• Alternative Title: DPP-4阻害薬であるビルダグリプチンは、非糖尿病アポリポタンパク質E欠損マウスの内皮機能障害と動脈硬化形成を軽減する; EFFECTS OF VILDAGLIPTIN ON ATHEROGENESIS
• Periodical title: International Heart Journal
• No. or year of volume/issue: 60 6
• Volume: 60
• Issue: 6
• Pages: 1421-1429
• ISSN (Periodical Title): ISSN : 1349-3299
• Degree grantor/type: 徳島大学
• Date Granted: 2020-03-23
• Dissertation Number: 甲第3354号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Diabetes mellitus; Endothelial function; Atherosclerosis; GLP-1; Endothelial Dysfunction; DPP-4 inhibitors
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1536/ihj.19-117
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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