ID | 114212 |
Title Alternative | 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
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Author |
Aini, Kunduziayi
Tokushima University
Tanaka, Kimie
The University of Tokyo
Higashikuni, Yasutomi
The University of Tokyo
Hirata, Yoichiro
The University of Tokyo
Yagi, Shusuke
Tokushima University
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Kusunose, Kenya
Tokushima University
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Yamada, Hirotsugu
Tokushima University
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Soeki, Takeshi
Tokushima University
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Sata, Masataka
Tokushima University
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Keywords | Diabetes mellitus
Endothelial function
Atherosclerosis
GLP-1
Endothelial Dysfunction
DPP-4 inhibitors
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
International Heart Journal
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ISSN | 13493299
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Publisher | International Heart Journal Association
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Volume | 60
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Issue | 6
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Start Page | 1421
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End Page | 1429
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Published Date | 2019-11-30
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Remark | 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 | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3354号
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Diploma Number | 甲医第1437号
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Granted Date | 2020-03-23
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
University Hospital
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