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 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.


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.
Ionita
Mihaela G
MG
UMC Utrecht, Laboratory of Experimental Cardiology, Room G02.523, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Vink
Aryan
A
Dijke
I Esmé
IE
Laman
Jon D
JD
Peeters
Wouter
W
van der Kraak
Petra Homoet
PH
Moll
Frans L
FL
de Vries
Jean-Paul P M
JP
Pasterkamp
Gerard
G
de Kleijn
Dominique P V
DP
D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016894:Endarterectomy, Carotid; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D012422:Rupture, Spontaneous
D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B