Association Between Myeloperoxidase Levels and Risk of Coronary Artery Disease

Zhang, Renliang; Brennan, Marie–Luise; Fu, Xiaoming; Aviles, Ronnier J.; Pearce, Gregory L.; Penn, Marc S.; Topol, Eric J.; Sprecher, Dennis L.; Hazen, Stanley L.

doi:10.1001/jama.286.17.2136

Cited by 832 publications

(570 citation statements)

References 52 publications

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“…Accordingly, MRS sensors for myelperoxidase (MPO), an enzyme associated with atherosclerosis and inflammation, 162 were designed as serotonin-labeled SPIO which become cross-linked in the presence of MPO. 107 Although not validated in vivo, these probes certainly take the first steps toward extending MRS-based probes into living subjects.…”

Section: Protein and Enzyme Detectionmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

et al. 2006

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Abstract-The field of molecular imaging has recently seen rapid advances in the development of novel contrast agents and the implementation of insightful approaches to monitor biological processes non-invasively. In particular, superparamagnetic iron oxide nanoparticles (SPIO) have demonstrated their utility as an important tool for enhancing magnetic resonance contrast, allowing researchers to monitor not only anatomical changes, but physiological and molecular changes as well. Applications have ranged from detecting inflammatory diseases via the accumulation of non-targeted SPIO in infiltrating macrophages to the specific identification of cell surface markers expressed on tumors. In this article, we attempt to illustrate the broad utility of SPIO in molecular imaging, including some of the recent developments, such as the transformation of SPIO into an activatable probe termed the magnetic relaxation switch.

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Section: Protein and Enzyme Detectionmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

et al. 2006

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“…18,38,39 Because rotenone exposure caused a notable increase in MPO expression, we sought to determine whether MPO could influence the ability of microglia to mediate cellular events in the rotenone-exposed brain. First, we investigated the effects of MPO on the viability of microglia.…”

Section: Mpo Enhances Production Of Ros and Inflammation-associated Mmentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

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“…MPO, released from activated leucocytes, catalyses the formation of HOCl from physiological concentrations of Cl − ions and H # O # (generated via the oxidative burst of leucocytes as well as other cells) [29]. It has been shown that both active MPO, and the products of its action, are present in various grades of human atherosclerotic lesion [22,24,30], and that the levels of this enzyme are strongly associated with coronary artery disease [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

Woods

Linton

Davies

2003

Biochemical Journal

107

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Oxidation is believed to play a role in atherosclerosis. Oxidized lipids, sterols and proteins have been detected in early, intermediate and advanced human lesions at elevated levels. The spectrum of oxidized side-chain products detected on proteins from homogenates of advanced human lesions has been interpreted in terms of the occurrence of two oxidative mechanisms, one involving oxygen-derived radicals catalysed by trace transition metal ions, and a second involving chlorinating species (HOCl or Cl2), generated by the haem enzyme myeloperoxidase (MPO). As MPO is released extracellularly by activated monocytes (and possibly macrophages) and is a highly basic protein, it would be expected to associate with polyanions such as the glycosaminoglycans of the extracellular matrix, and might result in damage being localized at such sites. In this study proteins extracted from extracellular matrix material obtained from advanced human atherosclerotic lesions are shown to contain elevated levels of oxidized amino acids [3,4-dihydroxyphenylalanine (DOPA), di-tyrosine, 2-hydroxyphenylalanine (o-Tyr)] when compared with healthy (human and pig) arterial tissue. These matrix-derived materials account for 83—96% of the total oxidized protein side-chain products detected in these plaques. Oxidation of matrix components extracted from healthy artery tissue, and model proteins, with reagent HOCl is shown to give rise to a similar pattern of products to those detected in advanced human lesions. The detection of elevated levels of DOPA and o-Tyr, which have been previously attributed to the occurrence of oxygen-radical-mediated reactions, by HOCl treatment, suggests an alternative route to the formation of these materials in plaques. This is believed to involve the formation and subsequent decomposition of protein chloramines.

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Association Between Myeloperoxidase Levels and Risk of Coronary Artery Disease

Abstract: Elevated levels of leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.

Cited by 832 publications

References 52 publications

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

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