Platelet-Derived TGF-1 Promotes Deep Vein Thrombosis

Thrombosis and haemostasis(2024)

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摘要
Background Transforming growth factor-beta 1 (TGF-beta 1) modulates multiple cellular functions during development and tissue homeostasis. A large amount of TGF-beta 1 is stored in platelet alpha-granules and released upon platelet activation. Whether platelet-derived TGF-beta 1 plays a role in venous thrombosis remains unclear. This study intends to assess the role of platelet-derived TGF-beta 1 in the development of venous thrombosis in mice.Material and methods TGF-beta 1(flox/flox) and platelet-specific TGF-beta 1(-/-) mice were utilized to assess platelet function in vitro, arterial thrombosis induced by FeCl3, tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), and deep vein thrombosis induced through ligation of the inferior vena cava (IVC). The IVC sample was collected to measure accumulation of neutrophils, monocytes, and the formation of neutrophil extracellular traps (NETs) by immunofluorescence staining.Results TGF-beta 1 deficiency in platelets did not affect the number of circulating platelets, platelet aggregation, adenosine triphosphate release, and integrin alpha IIb beta 3 activation. Meanwhile, TGF-beta 1 deficiency did not alter the arterial thrombus formation, hemostasis, and coagulation time (PT and APTT), but significantly impaired venous thrombus formation, inhibited the recruitment and accumulation of neutrophils and monocytes in thrombi, as well as reduced formation of NETs and platelet-neutrophil complex. In addition, adoptive transfer of TGF-beta 1(flox/flox) platelets to TGF-beta 1(-/-) mice rescued the impaired venous thrombus formation, recruitment of leukocytes and monocytes, as well as the NETs formation.Conclusion In conclusion, platelet-derived TGF-beta 1 positively modulates venous thrombus formation in mice, indicating that targeting TGF-beta 1 might be a novel approach for treating venous thrombosis without increasing the risk of bleeding.
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关键词
platelets,TGF-beta 1,venous thrombosis,neutrophils extracellular traps,bleeding
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