Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques

Fabio R Tavora,Mary Ripple,Allen P Burke,Ling Li

doi:10.1186/1471-2261-9-27

Abstract

BackgroundMyeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques.MethodsWe studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallory's Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed.ResultsMPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002)ConclusionUnstable fibrous caps are more likely to contain MPO-positive cells, neutrophils, and iron-containing macrophages than fibrous caps of stable fibroatheromas. MPO-positive cells in thrombi adjacent to disrupted plaques are associated with occlusive thrombi and are more numerous in diabetic patients.

Highlights

Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture
Plaque rupture is a major cause of coronary thrombosis, and is morphologically characterized by an interruption in a thin fibrous cap overlying a lipid rich core. [1,2,3,4] Often there are numerous macrophages infiltrating the fibrous cap of rupture plaques, suggesting a critical role in inciting plaque rupture
The purpose of this study was threefold: (1) to corroborate Sugiyama et al's and Naruko's finding that MPO positive cells including neutrophils are increased at the site of plaque instability; [5,6] (2) to quantitate MPO positive cells and neutrophils for the first time in thin-cap fibroatheroma; and (3) to correlate numbers of MPO positive cells in thrombi adjacent to ruptures with thrombus characteristics and risk factors

Summary

Introduction

Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. Myeloperoxidase (MPO) expressing monocytes and neutrophils have been described at the site of plaque disruption, suggesting a role of MPO in plaque rupture. [7,8] Recent evidence suggests that MPO-producing macrophages may persist in the atherosclerotic plaque and contribute to plaque instability. The purpose of this study was threefold: (1) to corroborate Sugiyama et al's and Naruko's finding that MPO positive cells including neutrophils are increased at the site of plaque instability; [5,6] (2) to quantitate MPO positive cells and neutrophils for the first time in thin-cap fibroatheroma; and (3) to correlate numbers of MPO positive cells in thrombi adjacent to ruptures with thrombus characteristics and risk factors Circulating monocytes produce hypochlorous acid by activation of MPO, increasing oxidative stress. [7,8] Recent evidence suggests that MPO-producing macrophages may persist in the atherosclerotic plaque and contribute to plaque instability. [9] In addition, serum levels of MPO seem to correlate with adverse risks in acute coronary syndrome patients.[10]

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