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

Persistent ID (NDL): info:ndljp/pid/11490181

Material type: 博士論文

Author: Aini, Kunduziayiほか

Publisher: International Heart Journal Association

Publication date: 2019-11-30

Material Format: Digital

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Name of awarding university/degree: 徳島大学,博士（医学）

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Note (General)：: Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initi...

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Material Type: 博士論文
ISSN: 1349-3299
Title: Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice
Volume: 60 6
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
Degree grantor/type: 徳島大学
Date Granted: 2020-03-23
Date Granted (W3CDTF): 2020-03-23
Dissertation Number: 甲第3354号
Degree Type: 博士（医学）
Conferring No. (Dissertation): 甲第3354号
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.
DOI: info:doi/10.1536/ihj.19-117
https://doi.org/info:doi/10.1536/ihj.19-117
Persistent ID (NDL): info:ndljp/pid/11490181
https://dl.ndl.go.jp/pid/11490181
Collection: 障害者向け資料
Collection (Materials For Handicapped People:1): テキストデータ
Collection (particular): 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
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2020-05-25T09:38:44+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
Availability of remote photoduplication service: 可
Periodical Title (URI): https://repo.lib.tokushima-u.ac.jp/114212
Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション
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