Endothelial Contributions to Venous Thrombus Resolution

Deep vein thrombosis (DVT) is an obstructive vascular condition with an incidence of ~1 in 1000 adults per year. Complications of DVT include post-thrombotic syndrome, which is debilitating and painful, and pulmonary embolism, which is life-threatening. Current treatments for DVT are associated with increased risks of bleeding, infection, or re-thrombosis, and fail to accelerate natural venous thrombus resolution. Venous thrombus resolution occurs through a process of organization that involves thrombus retraction away from the vein, fibrinolysis of the thrombus, and the formation of vascular channels within and around the thrombus. Endothelial cell (EC)-lined vascular channels are present in rodent and human resolving thrombi. Rodent models of DVT show that thrombus neovascularization occurs as early as 3-4 days after thrombus induction and increases progressively thereafter throughout thrombus resolution. The extent to which thrombus neovascularization contributes to its resolution, as well as the source of the ECs that vascularize the resolving thrombus, are unclear. Circumstantial evidence suggests that neovascularization is driven by resident ECs that ingress into the resolving thrombus, while circulating endothelial progenitor cells (EPCs) promote neovascularization in a paracrine manner. Resident ECs and EPCs also contribute to thrombus fibrinolysis. The aim of this review is to describe the role of ECs and EPCs in DVT resolution, and the potential of promoting thrombus endothelialization and vascularization for the treatment of DVT. We will also outline knowledge gaps in the understanding of EC/EPC-mediated contributions to DVT resolution. The promotion of EC-mediated thrombus resolution represents a novel therapeutic strategy for DVT.