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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1220.)
© 2009 American Heart Association, Inc.

Clinical and Population Studies

High Levels of Myeloid-Related Protein 14 in Human Atherosclerotic Plaques Correlate With the Characteristics of Rupture-Prone Lesions

Mihaela G. Ionita; Aryan Vink; I. Esmé Dijke; Jon D. Laman; Wouter Peeters; Petra Homoet van der Kraak; Frans L. Moll; Jean-Paul P.M. de Vries; Gerard Pasterkamp; Dominique P.V. de Kleijn

From the Experimental Cardiology Laboratory (M.G.I., W.P., G.P., D.P.V.d.K.) and the Departments of Pathology (A.V., P.H.v.d.K.) and Vascular Surgery (F.L.M.), University Medical Center Utrecht; the Department of Immunology (I.E.D., J.D.L.), Erasmus Medical Center Rotterdam; the Interuniversity Cardiology Institute of the Netherlands (ICIN) (W.P., D.P.V.d.K.), Utrecht; and the Department of Vascular Surgery (J.-P.P.M.d.V.), Saint Antonius Hospital, Nieuwegein, the Netherlands.

Correspondence to Dominique de Kleijn, PhD, UMC Utrecht, Laboratory of Experimental Cardiology, Room G02.523, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. E-mail d.dekleijn{at}umcutrecht.nl

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.

Conclusion— 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.

Key Words: S100A9 • vulnerable phaque • remodeling • macrophage • neutrophil