PMID:24691441

Citation	Wang, Y, Fang, C, Gao, H, Bilodeau, ML, Zhang, Z, Croce, K, Liu, S, Morooka, T, Sakuma, M, Nakajima, K, Yoneda, S, Shi, C, Zidar, D, Andre, P, Stephens, G, Silverstein, RL, Hogg, N, Schmaier, AH and Simon, DI (2014) Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis. J. Clin. Invest. 124:2160-71
Abstract	Expression of the gene encoding the S100 calcium-modulated protein family member MRP-14 (also known as S100A9) is elevated in platelets from patients presenting with acute myocardial infarction (MI) compared with those from patients with stable coronary artery disease; however, a causal role for MRP-14 in acute coronary syndromes has not been established. Here, using multiple models of vascular injury, we found that time to arterial thrombotic occlusion was markedly prolonged in Mrp14⁻/⁻ mice. We observed that MRP-14 and MRP-8/MRP-14 heterodimers (S100A8/A9) are expressed in and secreted by platelets from WT mice and that thrombus formation was reduced in whole blood from Mrp14⁻/⁻ mice. Infusion of WT platelets, purified MRP-14, or purified MRP-8/MRP-14 heterodimers into Mrp14⁻/⁻ mice decreased the time to carotid artery occlusion after injury, indicating that platelet-derived MRP-14 directly regulates thrombosis. In contrast, infusion of purified MRP-14 into mice deficient for both MRP-14 and CD36 failed to reduce carotid occlusion times, indicating that CD36 is required for MRP-14-dependent thrombosis. Our data identify a molecular pathway of thrombosis that involves platelet MRP-14 and CD36 and suggest that targeting MRP-14 has potential for treating atherothrombotic disorders, including MI and stroke.
Links	PubMed PMC4001535 Online version:10.1172/JCI70966
Keywords	Animals; Antigens, CD36/genetics; Antigens, CD36/metabolism; Blood Platelets/metabolism; Blood Platelets/pathology; Calgranulin B/genetics; Calgranulin B/metabolism; Calgranulin B/pharmacology; Carotid Artery Diseases/drug therapy; Carotid Artery Diseases/genetics; Carotid Artery Diseases/metabolism; Carotid Artery Diseases/pathology; Female; Gene Expression Regulation/genetics; Humans; Male; Mice, Knockout; Thrombosis/drug therapy; Thrombosis/genetics; Thrombosis/metabolism; Thrombosis/pathology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:S10A9		GO:0030194: positive regulation of blood coagulation	ECO:0000315:		P		In figure 3, MRP-14 deficiency reduces thrombus formation and size under flow, as well as collagen formation factors expressed.	complete CACAO 10154
MOUSE:S10A9		GO:0002543: activation of blood coagulation via clotting cascade	ECO:0000315:		P		In Figure 1D, the Mrp -/- phenotype shows stunted thrombus formation. Inferably, the protein Mrp +/+, or +/- where + is dominant, or its byproducts, cause thrombus formation.	complete CACAO 10155
MOUSE:S10A9	involved_in	GO:0030194: positive regulation of blood coagulation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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