By Robin Liang
PhD student at TREC
Venous thrombosis (VT) is a common yet complex disease, and the processes involved in its development are incompletely understood. Mouse models have been used to try to discover the mechanisms behind the disease. Recently, an international group of researchers published an article in the journal Blood about their findings in a particular mouse model of VT.
In this mouse model, the gene expression of the natural anticoagulant proteins antithrombin and protein C that help prevent clotting in normal situations was blocked using small interfering RNA (siRNA). The so-called “silencing” of these proteins by injection of siRNA led to VT formation without further invasive interventions. The researchers believe that this model is a good representation of a certain disease state of imbalanced coagulation that often results in VT in humans.
Previously, key players in the formation of venous thrombosis have been found using other mouse models. These include tissue factor (TF), platelets, factor XII (FXII), and neutrophils. In this paper, the scientists methodically used slightly different modifications to investigate the importance of each factor in their siRNA model. Mice deficient in FXII or neutrophils still suffered from VT to the same degree as control mice, suggesting that these factors are not crucial in development of VT in diseases with anticoagulant deficiency. On the other hand, they found that blocking TF or platelets successfully prevented VT in siRNA-treated mice, indicating that thrombus formation in this setting is dependent on these factors. The researchers thereby conclude that TF and platelets are the most important contributors to development of VT in their mouse model silencing natural anticoagulants.
Reference: Mouse venous trombosis upon silencing of anticoagulants depends on tissue factor and platelets, not FXII or neutrophils. Heestermans M et al. Blood. 2019; 133: 2090-2099.
