机构：[1]Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, the State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[2]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.[3]Clinical Laboratory, Hospital of University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China.四川省人民医院[4]Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[5]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[6]Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.[7]Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[8]Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[9]College of Mathematics, Sichuan University, Chengdu, Sichuan, China.[10]Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81673710]; NIH grant from the National Cancer Institute [CA177584]
第一作者机构：[1]Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, the State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.[2]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
通讯作者：
通讯机构：[1]Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, the State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.[2]Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.[9]College of Mathematics, Sichuan University, Chengdu, Sichuan, China.[10]Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
推荐引用方式(GB/T 7714)：
Guang Xin,Zeliang Wei,Chengjie Ji,et al.Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release[J].SCIENTIFIC REPORTS.2016,6:doi:10.1038/srep36222.
APA：
Guang Xin,Zeliang Wei,Chengjie Ji,Huajie Zheng,Jun Gu...&Wen Huang.(2016).Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release.SCIENTIFIC REPORTS,6,
MLA：
Guang Xin,et al."Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release".SCIENTIFIC REPORTS 6.(2016)
