Inhibitory Effects of Aspirin and Cilostazol on Intracellular Ca2+ Mobilization and Aggregation in Thrombin-activated Human Platelets

• Material Type: 博士論文
• Title: Inhibitory Effects of Aspirin and Cilostazol on Intracellular Ca2+ Mobilization and Aggregation in Thrombin-activated Human Platelets
• Author/Editor: Sone, Atsumi; Aki, Kensaku; Yasui, Toshiyuki; Hosoi, Eiji
• Author Heading: Sone, Atsumi; Aki, Kensaku; Yasui, Toshiyuki; Hosoi, Eiji
• Publication, Distribution, etc.: Tokushima University Faculty of Medicine
• Publication Date: 2023-02
• Publication Date (W3CDTF): 2023-02
• Alternative Title: トロンビン活性化ヒト血小板における細胞内Ca2+動員と凝集に対するアスピリンおよびシロスタゾールの抑制効果; Ca2+ Mobilization and Aggregation in Platelets
• Periodical title: The Journal of Medical Investigation
• No. or year of volume/issue: 70 1-2
• Volume: 70
• Issue: 1-2
• Pages: 94-100
• ISSN (Periodical Title): ISSN : 1349-6867; ISSN : 1343-1420
• Degree grantor/type: 徳島大学
• Date Granted: 2023-02-16
• Dissertation Number: 甲第3674号
• Degree Type: 博士（保健学）
• Text Language Code: eng
• Subject Heading: intracellular Ca2+ concentration; intensity of platelet aggregation; aspirin; cilostazol; thrombin
• Target Audience: 一般
• Note (General): Platelets play an important role in physiological hemostatic mechanisms. In contrast, platelet activation has been implicated in pathological conditions, such as atherosclerosis, angiogenesis, and inflammation. Thrombin is considered to be of particular pathological importance as a platelet-activating substance, and thrombin-activated platelets are detected in the blood of patients with advanced occlusive arterial disease. Ca2+ acts as a second messenger in platelet activation, and the regulation of intracellular Ca2+ concentrations ([Ca2+]i) is important for controlling platelet functions. However, changes in [Ca2+]i by antiplatelet agents remain unclear. Therefore, we herein investigated the relationship between [Ca2+]i and the intensity of platelet aggregation after a thrombin stimulation, the relationship between [Ca2+]i and the intensity of platelet aggregation by antiplatelet agents, and the effects of antiplatelet agents on thrombin-activated platelets as a surrogate platelet model for arterial occlusive disease. Fura2-loaded platelets were treated with phosphate-buffered saline or a low concentration of thrombin (0.005 U/mL), followed by antiplatelet agents (aspirin or cilostazol), and changes in [Ca2+]i and the intensity of platelet aggregation by the thrombin stimulation were measured using fluorescence spectrophotometry. Changes in [Ca2+]i and the intensity of platelet aggregation after the thrombin stimulation as well as the relationship between [Ca2+]i and the intensity of platelet aggregation by antiplatelet agents indicated that cilostazol exerted stronger antiplatelet effects than aspirin and also that antiplatelet effects may be attenuated in thrombin-activated platelets. The present results also suggest the utility of thrombin-activated platelets as a surrogate platelet model for arterial occlusive disease. These results may contribute to future drug development for antiplatelet therapy.
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.2152/jmi.70.94
• 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

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http://repo.lib.tokushima-u.ac.jp/files/public/11/118198/20230510152456768594/k3674_abstract.pdf fulltext

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