Immune cell-mediated venous thrombus resolution

Abstract

Herein, we review the current processes that govern experimental deep vein thrombus (DVT) resolution. How the human DVT resolves at the molecular and cellular level is not well known due to limited specimen availability. Experimentally, the thrombus resolution resembles wound healing, with early neutrophil-mediated actions followed by monocyte/macrophage-mediated events, including neovascularization, fibrinolysis, and eventually collagen replacement. Potential therapeutic targets are described, and coupling with site-directed approaches to mitigate off-target effects is the long-term goal. Similarly, timing of adjunctive agents to accelerate DVT resolution is an area that is only starting to be considered. There is much critical research that is needed in this area.

Keywords: deep vein thrombosis; fibrinolysis; inflammation; leukocytes; venous thrombosis.

Figure

Global mechanism of thrombus resolution via mediators and the immune system cells. Early neutrophils invade the thrombus, promoting thrombogenesis and then early lysis. T-cells trigger the activation of proinflammatory macrophages via IFNγ, inhibiting macrophages from switching into the proresolving phenotype. Over time, proinflammatory macrophages likely transition to become proresolving macrophages, at which point they promote fibrinolysis, angiogenesis, and collagenolysis via various mediators. IFNγ, interferon gamma; IL, interleukin; MMP, matrix metalloproteinase; PAI-1, plasminogen activator inhibitor; TGFb, transforming growth factor-beta; TLR, toll-like receptor; uPA, urokinase plasminogen activator; VEGF, vascular endothelial growth factor.