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

• 資料種別: 博士論文
• ISSN: 1349-3299
• タイトル: Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice
• 巻次・部編番号: 60 6
• 著者・編者: Aini, Kunduziayi; Fukuda, Daiju; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Sata, Masataka
• 著者標目: Aini, Kunduziayi; Fukuda, Daiju; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Sata, Masataka
• 出版事項: International Heart Journal Association
• 出版年月日等: 2019-11-30
• 出版年（W3CDTF）: 2019-11-30
• 並列タイトル等: 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
• タイトル（掲載誌）: International Heart Journal
• 授与機関名: 徳島大学
• 授与年月日: 2020-03-23
• 授与年月日（W3CDTF）: 2020-03-23
• 報告番号: 甲第3354号
• 学位: 博士（医学）
• 博論授与番号: 甲第3354号
• 本文の言語コード: eng
• 件名標目: Diabetes mellitus; Endothelial function; Atherosclerosis; GLP-1; Endothelial Dysfunction; DPP-4 inhibitors
• 対象利用者: 一般
• 一般注記: 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.
• DOI: info:doi/10.1536/ihj.19-117; https://doi.org/info:doi/10.1536/ihj.19-117
• 国立国会図書館永続的識別子: info:ndljp/pid/11490181; https://dl.ndl.go.jp/pid/11490181
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 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
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2020-05-25T09:38:44+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: https://repo.lib.tokushima-u.ac.jp/114212
• 連携機関・データベース: 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