A new target for prevention of blood clots?

Av Robin Liang
Stipendiat ved TREC

Platelets play a role in the formation of blood clots, but the impact of their different receptors is still unclear. CLEC-2 is among the receptors found on platelets, and is important in maintaining the normal state of vessels in the presence of inflammation. As deep vein thrombosis (DVT) is a thromboinflammatory disorder involving a blood clot in the deep veins of the leg, CLEC-2 could be a receptor of interest in DVT research.

In an article recently published in Blood, a research group in Birmingham created a series of animal experiments to investigate the role of CLEC-2 in DVT formation. The mice underwent an operation restricting blood flow in the inferior vena cava (IVC), the main vein leading blood back to the heart. This is a widely-used model for DVT in mice. They found that mice with induced loss of CLEC-2 were completely protected from DVT. Platelet-specific CLEC-2 knockout mice (mice bred to lack CLEC-2 on their platelets) had a significantly lower prevalence of DVT than their control littermates, and their clots were smaller than those in control mice. Some knockout mice lacking platelet-specific CLEC-2 were transfused with platelets with CLEC-2 from normal mice; these mice developed thrombi as often as controls. These experiments all support the importance of CLEC-2 in DVT development.

Podoplanin, the protein that binds to CLEC-2, had previously been found on lymph vessels and tumor cells, but not on blood vessels. The research group  found that podoplanin is expressed in the IVC vessel wall and the amount of increased expression corresponded to the degree of thrombosis.

The researchers also injected anti-podoplanin blocking antibody into mice, but did not find a lower prevalence of DVT. However, both the weight and the length of the clots were significantly lower in antibody-treated animals than controls. In another experiment, they found that platelet recruitment to the vessel wall in these animals was diminished to a similar level as in mice lacking the platelet-specific CLEC-2 receptor.

While the researchers show that both CLEC-2 receptor and podoplanin play a role in the initiation of DVT, the mechanisms remain unclear. More research is needed, but they propose CLEC-2 may be a new potential target for the prevention of DVT.

Referanse: Payne H, Ponomaryov T, Watson SP, Brill A. Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis. Blood (April 2017).

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