アクセス数 : ?
ダウンロード数 : ?
ID 114201
タイトル別表記
P2Y12阻害薬チカグレロールはアポリポ蛋白E欠損マウスの血管障害を軽減して動脈硬化形成を抑制する
著者
ガンバートル, ビヤンバスレン 徳島大学大学院医科学教育部(医学専攻)
Salim, Hotimah Masdan Tokushima University
Nishimoto, Sachiko Tokushima University
Tanaka, Kimie The University of Tokyo
Higashikuni, Yasutomi The University of Tokyo
Hirata, Yoichiro The University of Tokyo
キーワード
Atherosclerosis
Inflammation
Endothelial function
P2Y12
Ticagrelor
資料タイプ
学位論文
抄録
Background and aims: Ticagrelor reduces cardiovascular events in patients with acute coronary syndrome (ACS). Recent studies demonstrated the expression of P2Y12 on vascular cells including endothelial cells, as well as platelets, and suggested its contribution to atherogenesis. We investigated whether ticagrelor attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein E-deficient (apoe-/-) mice.
Methods: Eight-week-old male apoe-/- mice were fed a western-type diet (WTD) supplemented with 0.1% ticagrelor (approximately 120 mg/kg/day). Non-treated animals on WTD served as control. Atherosclerotic lesions were examined by en-face Sudan IV staining, histological analyses, quantitative RT-PCR analysis, and western blotting. Endothelial function was analyzed by acetylcholine-dependent vasodilation using aortic rings. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments.
Results: Ticagrelor treatment for 20 weeks attenuated atherosclerotic lesion progression in the aortic arch compared with control (p < 0.05). Ticagrelor administration for 8 weeks attenuated endothelial dysfunction (p < 0.01). Ticagrelor reduced the expression of inflammatory molecules such as vascular cell adhesion molecule-1, macrophage accumulation, and lipid deposition. Ticagrelor decreased the phosphorylation of JNK in the aorta compared with control (p < 0.05). Ticagrelor and a JNK inhibitor ameliorated impairment of endothelium-dependent vasodilation by adenosine diphosphate (ADP) in wild-type mouse aortic segments. Furthermore, ticagrelor inhibited the expression of inflammatory molecules which were promoted by ADP in HUVEC (p < 0.001). Ticagrelor also inhibited ADP-induced JNK activation in HUVEC (p < 0.05).
Conclusions: Ticagrelor attenuated vascular dysfunction and atherogenesis through the inhibition of inflammatory activation of endothelial cells. These effects might be a potential mechanism by which ticagrelor decreases cardiovascular events in patients with ACS.
掲載誌名
Atherosclerosis
ISSN
00219150
cat書誌ID
AA00553457
AA11522036
出版者
Elsevier
275
開始ページ
124
終了ページ
132
発行日
2018-05-31
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Byambasuren Ganbaatar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3353号
学位記番号
甲医第1436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