Abstract 5171: High Levels of Myeloid-related Protein 14 in Human Atherosclerotic Plaques Correlate With the Characteristics of Rupture-prone Lesions
Objective: Atherosclerotic plaque rupture can lead to severe complications such as myocardial infarction and stroke. Myeloid related protein (Mrp)-14, Mrp-8 and Mrp-8/14 complex are inflammatory markers associated with myocardial infarction. It is, however, unknown if Mrps are associated with a rupture-prone plaque phenotype. In this study, we determined the association between Mrp-14, -8, -8/14 plaque levels and plaque characteristics.
Methods and Results: In 186 human carotid plaques, levels of Mrp-14, -8 and -8/14 were quantified using ELISA. High levels of Mrp-14 were found in lesions with a large lipid core, high macrophage staining and low smooth muscle cell and collagen amount. Plaques with high levels of Mrp-14 contained high interleukin (IL)-6, IL-8, matrix metalloprotease (MMP)-8, MMP-9 and low MMP-2 concentrations. Mrp-8 and Mrp-8/14 showed a similar trend. Within plaques, a subset of non-foam macrophages expressed Mrp-8 and Mrp-14 and the percentage of Mrp-positive macrophages was higher in rupture-prone lesions compared to stable ones. In vitro, this subset of macrophages does not acquire a foamy phenotype when fed with human oxidized low density lipoprotein (oxLDL). In contrast, the vast majority of macrophages lacking Mrp-8/14 membrane expression accumulated lipid droplets in the cytoplasm when fed with oxLDL.
Conclusion: High levels of Mrp-14 and to a lesser extent also Mrp-8 and Mrp-8/14, expressed by a subset of non-foam macrophages in human plaques, are strongly associated with both histopathological features and the inflammatory status of rupture prone lesions. These results identify Mrps as possible imaging markers to detect the hidden rupture-prone plaque.