Myeloid-related protein-8/14 in acute coronary syndrome

Background The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS). Methods and results In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R2=0.52), but not with soluble P-selectin level (R2=0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression. Conclusions Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS.