Transforming Growth Factors in Venous Thrombus Formation and Resolution

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.