Metformin prevented both venous and arterial thrombosis without significantly prolonging bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA release.
p-value: p=<0.05
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.
Xin et al. (Wed,) conducted a other in Thrombosis and Type 2 Diabetes Mellitus. Metformin vs. Vehicle control or aspirin was evaluated on Arterial and venous thrombus formation and platelet activation (p=<0.05). Metformin prevented both venous and arterial thrombosis without significantly prolonging bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA release.