| First Author | Wang Y | Year | 2014 |
| Journal | J Clin Invest | Volume | 124 |
| Issue | 5 | Pages | 2160-71 |
| PubMed ID | 24691441 | Mgi Jnum | J:213163 |
| Mgi Id | MGI:5582990 | Doi | 10.1172/JCI70966 |
| Citation | Wang Y, et al. (2014) Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis. J Clin Invest 124(5):2160-71 |
| abstractText | 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. |
