Ticagrelor, a P2Y12 antagonist, attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein-E-deficient mice

• Material Type: 博士論文
• Title: Ticagrelor, a P2Y12 antagonist, attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein-E-deficient mice
• Author/Editor: Ganbaatar, Byambasuren; Fukuda, Daiju; Salim, Hotimah Masdan; Nishimoto, Sachiko; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Yagi, Shusuke; Soeki, Takeshi; Sata, Masataka
• Author Heading: Ganbaatar, Byambasuren; Fukuda, Daiju; Salim, Hotimah Masdan; Nishimoto, Sachiko; Tanaka, Kimie; Higashikuni, Yasutomi; Hirata, Yoichiro; Yagi, Shusuke; Soeki, Takeshi; Sata, Masataka
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2018-05-31
• Publication Date (W3CDTF): 2018-05-31
• Alternative Title: 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
• Periodical title: Atherosclerosis
• No. or year of volume/issue: 275
• Volume: 275
• Pages: 124-132
• ISSN (Periodical Title): ISSN : 0021-9150
• Degree grantor/type: 徳島大学
• Date Granted: 2020-03-23
• Dissertation Number: 甲第3353号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Atherosclerosis; Inflammation; Endothelial function; P2Y12; Ticagrelor
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.atherosclerosis.2018.05.053
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

Table of Contents

https://repo.lib.tokushima-u.ac.jp/files/public/11/114201/20200414170733490254/k3353_abstract_review.pdf fulltext

https://repo.lib.tokushima-u.ac.jp/files/public/11/114201/20200414170733987437/k3353_fulltext.pdf fulltext