Metformin Serves as a Novel Drug Treatment for Arterial Thrombosis: Inhibitory Mechanisms on Collagen-Induced Human Platelet Activation

Please use this identifier to cite or link to this item: http://140.112.115.32:8080/ir/handle/987654321/2807

Title:	Metformin Serves as a Novel Drug Treatment for Arterial Thrombosis: Inhibitory Mechanisms on Collagen-Induced Human Platelet Activation
Authors:	Chang, Yi;Huang, Wei Chieh;Hsu, Chia Yuan;Hsia, Chih Wei;Jayakumar, Thanasekaran;Hsieh, Cheng Ying;Lu, Wan Jung;Chang, Chao Chien
Contributors:	視光學系
Keywords:	human platelets;metformin;p38 MAPK;PLCγ2;pulmonary thrombosis;PI3K/Akt/GSK3β;type 2 diabetes
Date:	2022-07-01
Issue Date:	2025-08-11 14:44:13 (UTC+8)
Abstract:	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.
Relation:	Applied Sciences-Basel, 12. https://doi.org/10.3390/app12157426
Appears in Collections:	[Department of Optometry] Journal

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