Supporting Roles of Platelet Thrombospondin-1 and CD36 in Thrombus Formation on Collagen

Abstract

Objective— Platelets abundantly express the membrane receptor CD36 and store its ligand thrombospondin-1 (TSP1) in the α-granules. We investigated whether released TSP1 can support platelet adhesion and thrombus formation via interaction with CD36. Approach and Results— Mouse platelets deficient in CD36 showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression. Deficiency in either CD36 or TSP1 resulted in markedly increased dissolution of thrombi formed on collagen, although thrombus buildup was unchanged. In mesenteric vessels in vivo, deficiency in CD36 prolonged the time to occlusion and enhanced embolization, which was in agreement with earlier observations in TSP1-deficient mice. Thrombi formed using wild-type blood stained positively for secreted TSP1. Releasate from wild-type but not from TSP1-deficient platelets enhanced platelet activation, phosphatidylserine expression, and thrombus formation on collagen. The enhancement was dependent on CD36 because it was without effect on thrombus formation by CD36-deficient platelets. Conclusions— These results demonstrate an anchoring role of platelet-released TSP1 via CD36 in platelet adhesion and collagen-dependent thrombus stabilization. Thus, the TSP1–CD36 tandem is another platelet ligand–receptor axis contributing to the maintenance of a stable thrombus.

Platelet CD40L Modulates Thrombus Growth Via Phosphatidylinositol 3-Kinase β, and Not Via CD40 and IκB Kinase α

“…Stimulation with ADP resulted in high α IIb β 3 activation, but not in α-granule secretion, as previously demonstrated. 25 Taken together, these results suggest that, in Apoe −/− mice, platelet CD40L and CD40 play nonidentical roles in GPVI-induced integrin activation and α-granule secretion.…”

Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade

“…Plasma-and platelet-derived TSP-1 contributes to physiological platelet adhesion and platelet endothelial crosstalk. 33,37 In contrast, endothelial-derived microparticles, advanced glycation end products, and MRP14 can drive thrombosis. [38][39][40] Platelet hyperactivity that underpins arterial thrombosis in the context of dyslipidemia is thought to proceed through the actions of oxLDL.…”

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

“…21,22 On the other hand, TSP1 has also been suggested to act as a reductase that controls VWF multimer size, and thereby may negatively regulate thrombus growth. 22,23 Second, TSP1 could directly interact with its counter receptors on platelets, particularly CD36, 20 to mediate platelet adhesion under arterial shear and thereby promote thrombosis. Although these studies suggest VWF dependent and independent roles for TSP1 in arterial thrombosis, definitive in vivo evidence for either was still lacking.…”

“…20 On the other hand, TSP1 has been shown to compete with ADAMTS13 for binding A2 and A3 domains of VWF, thus protecting it from proteolytic cleavage. 21 TSP1 has also been shown to regulate multimer size of circulating VWF, or VWF released from activated platelets.…”