馬偕醫學大學機構典藏(MacKay Medical University Institutional Repository):Item 987654321/2807
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题名: Metformin Serves as a Novel Drug Treatment for Arterial Thrombosis: Inhibitory Mechanisms on Collagen-Induced Human Platelet Activation
作者: Yi Chang;Wei Chieh Huang;Chia Yuan Hsu;Chih Wei Hsia;Thanasekaran Jayakumar;Cheng Ying Hsieh;Wan Jung Lu;Chao Chien Chang
贡献者: 視光學系
关键词: human platelets;metformin;p38 MAPK;PLCγ2;pulmonary thrombosis;PI3K/Akt/GSK3β;type 2 diabetes
日期: 2022-07-01
上传时间: 2025-08-11 14:44:13 (UTC+8)
摘要: Metformin is widely used as first-line medication for type 2 diabetes (T2D), the main disease comorbid with kidney disease, cardiovascular diseases (CVDs), and retinopathy. Platelets are crucial in platelet-dependent arterial thrombosis, which causes CVDs and cerebrovascular diseases. Research indicates that metformin may improve these diseases; metformin reportedly reduced platelet activation in rats. However, no reports have included human platelets. We investigated the mechanisms underlying metformin’s effects on platelet activation by using human platelets and evaluated its in vivo effectiveness in experimental mice. Metformin inhibited platelet aggregation stimulated by collagen but not by arachidonic acid, U46619, or thrombin. Metformin suppressed ATP release, [Ca2+]i mobilization, and P-selectin expression, as well as phospholipase C (PLC)γ2/protein kinase C (PKC), p38 mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) phosphorylation. Metformin did not affect vasodilator-stimulated phosphoprotein (VASP) phosphorylation. In the animal studies, metformin reduced acute pulmonary thromboembolism mortality without increasing bleeding times. These results provide insights into the role and mechanisms of metformin in human platelet activation. Metformin decreased platelet activation by interfering with the PLCγ2/PKC, PI3K/Akt/GSK3β, and p38 MAPK pathways through a VASP-independent mechanism. Metformin demonstrates promise as a new class of antiplatelet agent that can inhibit platelet activation.
關聯: Applied Sciences-Basel, 12(15), 7426. https://doi.org/10.3390/app12157426
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