徳島大学 教育・研究者情報データベース(EDB)

1. (英) Ganbaatar B / (日) GANBAATAR BYAMBASUREN / (読) がんばとる びやんばすれん

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2. 福田 大受

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3. (英) Salim HM

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4. (英) Nishimoto Sachiko / (日) 西本 幸子 / (読) にしもと さちこ

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5. (英) Tanaka K

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6. (英) Higashikuni Y

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7. (英) Hirata Y

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8. 八木 秀介

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9. 添木 武([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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10. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

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

(英) 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. 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. 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). 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.

1. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

1. (英) Article.ELocationID: S0021-9150(18)30296-X

2. (英) Article.ELocationID: 10.1016/j.atherosclerosis.2018.05.053

3. (英) Article.PublicationTypeList.PublicationType: Journal Article

4. (英) KeywordList.Keyword: Atherosclerosis

5. (英) KeywordList.Keyword: Endothelial function

6. (英) KeywordList.Keyword: Inflammation

7. (英) KeywordList.Keyword: P2Y12

8. (英) KeywordList.Keyword: Ticagrelor