Platelet Serotonin in Arterial and Deep Vein Thrombosis

Objectives: Large amounts of peripheral serotonin are stored in dense granules of circulating blood platelets. Serotonin is well known as a vasoactive mediator and platelet activator in hemostasis. In the recent years it also became an immunomodulatory role in inflammation by influencing the recruitment of leukocytes, especially neutrophils. Now, that we know, that there is a kind of immunothrombosis, its role in in the development of arterial and deep vein thrombosis needs to be investigated deeper.

In this work we want to investigate the role of peripheral serotonin on the development on arterial and deep vein thrombosis in different mouse models.

Methods: To study arterial thombosis we used different mouse models (Laser injury in mesenteric arteries, mechanical injury in the abdominal aorta and chemical injury (FeCl₃) in the cartotid artery). 6-8 week old C57Bl/6 and Tph1-/- (Tryptophane hydroxylase 1) mice, lacking peripheral serotonin, were investigated in the mentioned thrombosis models. The time to occlusion was measured as outcome parameter.

To study the role of serotonin in deep vein thrombosis, the stenosis model of the vena cava inferior was used. Therefor a 90% stenosis of the infrarenal vena cava inferior was performed. 4-6 week-old C57Bl/6, SSRI-treated C57Bl/6 (depleated serotoninpools in platelets), SERT-/- (serotonin-transporter) and Tph1-/- underwent the mentioned vena cava inferior stenosis. 48 hours later the thrombus was harvested with the surrounding vena cava inferior. Thrombus volume was measured. Thrombus composition was analyzed using immunofluorescence microscopy. Platelet-neutrophil and platelet-monocyte complexes were analyzed in peripheral blood.

Results: In Tph1-/- mice arterial thrombi occured later in mesenteric arteries (7.2±1.48 vs. 8.95±3.29 min, p=0.064) and time to occlusion was delayed significantly in mesenteric arteries (14.09±4.91 vs. 19.99±6.14 min, p=0.01), the abdominal aorta (245.9±72.4 vs. 429.6±188.3 sec, p=0.003) and the carotid artery (223.8±30.3 vs. 452.2±176.9 sec, p=0.02).

So far the results of the deep vein thrombosis models are pending. But we are optimistic, that we will have the results until the GTH Congress starts.

Conclusion: The lack of peripheral serotonin delays the onset and time to occlusion in arterial thrombus formation. This is not surprising, as we know that arterial thrombi depend on the activation of platelets. We think that the composition of venous thrombi may be influenced by the lack of peripheral serotonin, as it influences the formation of platelet-leukocyte complexes and thereby the recruitment of immune cells to inflammatory environments.