Abstract 17044: Myeloid-Related Protein 8/14 Implicated in Atherothrombosis According to Activated Leukocyte
Objectives: MRP-14 (S100A9) has been identified by platelet transcriptional profiling as an acute myocardial infarction gene. MRP-14, a member of the S100- family of calcium-modulated proteins, also broadly regulates vascular inflammation. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. However, a role for MRP-8/14 in acute coronary syndromes (ACS) is largely undefined. The aim of this study was to elucidate clinical and biological significance of MRP-8/14 in patients with ACS.
Methods and Results: Plasma levels of MRP-8/14 were measured in 21 patients with ACS and 10 patients with stable coronary artery disease (CAD) using peripheral venous blood samples. MRP-8/14 levels was higher in ACS compared to stable CAD (10.7 vs. 6.4 mcg/L, P=0.033). In 38 consecutive ACS patients, coronary artery MRP-8/14 level was measured using thrombectomy catheter aspiration at the site of the culprit lesion. MRP-8/14 concentration was significantly higher in 23 patients with visible aspirated thrombus compared to the 15 patients without thrombus (5.7 vs. 3.4 mcg/L, P=0.049). In these coronary artery samples, MRP-8/14 concentration correlated with myeloperoxidase (MPO) level, but not with levels of soluble P-selectin. Finally, expression of MRP8/14 was also examined using immunohistochemistry of aspirated thrombus. MRP-8/14 co-localized with CD11b-positive leukocytes but not glyocoprotein IIb-positive platelets. In the cultured human umbilical vein endothelial cells (HUVEC), MRP-8/14 stimulated to increase the tissue factor (TF) concentration in the cultured medium, compared to phosphate buffered saline (PBS), as control.
Conclusion: The findings indicate that MRP-8/14 is elevated in patients with ACS compared to stable CAD, that MRP-8/14 concentration is higher in coronary artery blood containing thrombus, and leukocytes is the likely sources of secreted MRP-8/14 at the sites of culprit lesions. MRP-8/14 implicated in atherothrombosis according to activated leukocyte. Thus, MRP-8/14 is positioned as a unique biomarker and likely target in atherothrombosis.
- © 2013 by American Heart Association, Inc.