Davis Jonathan, Maranto Molly, Kennedy Jonathan, Wang Xiaoqin, Azhar Mohamad, Jain Abhishek, Evans Colin E
Cardiovascular Translational Research Center (J.D., C.E.E.), University of South Carolina School of Medicine, Columbia.
Department of Pharmacology, Physiology and Neuroscience (M.M.), University of South Carolina School of Medicine, Columbia.
Arterioscler Thromb Vasc Biol. 2025 May;45(5):643-653. doi: 10.1161/ATVBAHA.124.322395. Epub 2025 Mar 20.
Deep vein thrombosis (DVT) and pulmonary embolism are vascular occlusive disorders categorized under the term venous thromboembolism. Venous thromboembolism affects ≈900 000 people per year in the United States alone. Understanding of the multifaceted process of DVT has improved in recent years, and current DVT treatments reduce thrombus propagation, but they also increase bleeding risk and fail to accelerate natural venous thrombus resolution. Multiple inflammatory cytokines regulate the development and subsequent resolution of DVT. One family of cytokines involved in DVT and venous thrombus resolution is the TGF-β (transforming growth factor-β) family. A comprehensive understanding of the control of venous thrombus formation and resolution by the TGF-β family could lead to the development of novel treatments for DVT that target ≥1 of the TGF-β isoforms. The aim of this review is to describe studies of the roles of the TGF-β isoforms in venous thrombus formation and resolution and to highlight opportunities for future research. TGF-β isoforms include TGF-β1, TGF-β2, and TGF-β3. TGF-β1 has a well-characterized role in the positive regulation of venous thrombus formation and the negative regulation of venous thrombus resolution. Further research is necessary, however, to understand the potential roles of TGF-β2 and TGF-β3 in venous thrombus formation and resolution. Given that TGF-β1 expression increases during venous thrombosis and that inhibition or knockdown of TGF-β1 reduces thrombus burden, TGF-β1 represents a potential diagnostic marker for DVT and a putative target for therapies that aim to prevent or treat DVT.
深静脉血栓形成（DVT）和肺栓塞属于血管闭塞性疾病，归类于静脉血栓栓塞这一术语范畴。仅在美国，每年就有大约90万人受到静脉血栓栓塞的影响。近年来，对DVT多方面形成过程的认识有所提高，目前的DVT治疗可减少血栓扩展，但也会增加出血风险，且无法加速天然静脉血栓的溶解。多种炎性细胞因子调节DVT的发生及后续溶解过程。参与DVT和静脉血栓溶解的一类细胞因子是转化生长因子-β（TGF-β）家族。全面了解TGF-β家族对静脉血栓形成和溶解的调控，可能会促使开发针对一种或多种TGF-β亚型的新型DVT治疗方法。本综述的目的是描述TGF-β亚型在静脉血栓形成和溶解中作用的研究，并突出未来研究的机会。TGF-β亚型包括TGF-β1、TGF-β2和TGF-β3。TGF-β1在静脉血栓形成的正向调节和静脉血栓溶解的负向调节中具有明确的作用。然而，需要进一步研究以了解TGF-β2和TGF-β3在静脉血栓形成和溶解中的潜在作用。鉴于TGF-β1在静脉血栓形成过程中表达增加，且抑制或敲低TGF-β1可减轻血栓负荷，TGF-β1代表了DVT的一种潜在诊断标志物以及旨在预防或治疗DVT的疗法的假定靶点。
