High levels of myeloid-related protein 14 in human atherosclerotic plaques correlate with the characteristics of rupture-prone lesions

Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1220-7. doi: 10.1161/ATVBAHA.109.190314. Epub 2009 Jun 11.

Abstract

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 whether 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 nonfoam 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 oxLDL.

Conclusions: Mrp-14 is strongly associated with the histopathologic features and the inflammatory status of rupture-prone atherosclerotic lesions, identifying Mrp-14 as a local marker for these plaques.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Atherosclerosis / surgery
  • Biomarkers / metabolism
  • Calgranulin A / metabolism
  • Calgranulin B / metabolism*
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology*
  • Carotid Artery Diseases / metabolism*
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / surgery
  • Endarterectomy, Carotid
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Macrophages / pathology
  • Retrospective Studies
  • Rupture, Spontaneous

Substances

  • Biomarkers
  • Calgranulin A
  • Calgranulin B