Crosstalk between thrombospondin-1 and CD36 modulates platelet-RBC interaction limiting thrombosis and abdominal aneurysm formation

Krott, K. J.; Feige, T.; Bosbach, A.; Beele, A.; Krueger, I.; Reusswig, F.; Schickentanz-Dey, E.; Chadt, A.; Kelm, M.; Gerdes, N.; Pfeiler, S.; Jurk, K.; Kiouptsi, K.; Reinhardt, C.; Al-Hasani, H.; Kehrel, B.; Karray, S.; Schelzig, H.; Wagenhaueser, M.; Elvers, M.

doi:10.1101/2024.03.18.585356

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bioRxiv · 10.1101/2024.03.18.585356

Crosstalk between thrombospondin-1 and CD36 modulates platelet-RBC interaction limiting thrombosis and abdominal aneurysm formation

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Abstract

Red blood cells (RBCs) contribute to hemostasis and thrombosis by interaction with platelets via the FasL-FasR pathway to induce procoagulant activity and thrombin formation. Here, we identified a novel mechanism of platelet-RBC interaction via the CD36-thrombospondin-1 (TSP-1) signaling pathway, which is important in thrombus formation and the recruitment of RBCs to collagen-adherent platelets. Platelet-released TSP-1 can bind to CD36 at the RBC membrane to enhance procoagulant activity and to increase the activation of integrin IIb{beta}3, which represents an additional ligand for erythroid FasR, suggesting that both mechanisms of platelet-RBC interaction act in concert to propagate thrombus formation. In patients with abdominal aortic aneurysm (AAA), enhanced procoagulant activity of RBCs and platelets is accompanied by elevated exposure of TSP-1 and FasL at the platelet surface and accumulation of TSP-1 in the aortic wall and the intraluminal thrombus, suggesting that platelet-RBC interaction plays an important role in AAA pathology. TSP-1-deficient mice are protected against aortic diameter expansion in an experimental model of AAA, highlighting the crucial role of the CD36-TSP-1 axis in AAA. Thus, interfering with platelet-RBC interaction may be a promising therapeutic approach to reduce pro-coagulant activity and preserve AAA patients from surgery or rupture.

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Krott, K. J., Feige, T., Bosbach, A., Beele, A., Krueger, I., Reusswig, F., Schickentanz-Dey, E., Chadt, A., Kelm, M., Gerdes, N., Pfeiler, S., Jurk, K., Kiouptsi, K., Reinhardt, C., Al-Hasani, H., Kehrel, B., Karray, S., Schelzig, H., Wagenhaueser, M., Elvers, M.. 2024-03-19. Crosstalk between thrombospondin-1 and CD36 modulates platelet-RBC interaction limiting thrombosis and abdominal aneurysm formation. https://doi.org/10.1101/2024.03.18.585356

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