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ID 114212
タイトル別表記
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
著者
アイニ, クンドウズアイ 徳島大学大学院医科学教育部(医学専攻)
Tanaka, Kimie The University of Tokyo
Higashikuni, Yasutomi The University of Tokyo
Hirata, Yoichiro The University of Tokyo
キーワード
Diabetes mellitus
Endothelial function
Atherosclerosis
GLP-1
Endothelial Dysfunction
DPP-4 inhibitors
資料タイプ
学位論文
抄録
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.
掲載誌名
International Heart Journal
ISSN
13493299
出版者
International Heart Journal Association
60
6
開始ページ
1421
終了ページ
1429
発行日
2019-11-30
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Kunduziayi Ainiの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3354号
学位記番号
甲医第1437号
学位授与年月日
2020-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院