A functional myeloperoxidase polymorphic variant is associated with coronary artery disease in French-Canadians

Nikpoor, Borzoo; Turecki, Gustavo; Fournier, Caroline; Théroux, Pierre; Rouleau, Guy A.

doi:10.1067/mhj.2001.116769

Cited by 195 publications

(140 citation statements)

References 7 publications

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“…37 Myeloperoxidase deficiency is associated with decreased frequency of cardiovascular events, 38 and functional polymorphisms in the myeloperoxidase gene that lead to decreased enzyme expression confer cardioprotection. 39 The present studies thus provide additional support, albeit indirect, for the hypothesis that myeloperoxidase-generated oxidants are involved in the pathogenesis of cardiovascular disease.…”

Section: Discussionsupporting

confidence: 56%

Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory Pathways

et al. 2003

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Background-The pleiotropic actions of hydroxymethylglutaryl CoA reductase inhibitors (statins) include antiinflammatory and antioxidant actions. We recently reported that statins induce reductions in plasma protein levels of nitrotyrosine (NO 2 Tyr), a modification generated by nitric oxide-derived oxidants. Whether alternative oxidative pathways are suppressed in vivo after statin administration has not yet been reported. Methods and Results-As an extension of our prior study, hypercholesterolemic subjects with no known coronary artery disease were evaluated at baseline and after 12 weeks of atorvastatin therapy (10 mg/d). Plasma levels of protein-bound chlorotyrosine, NO 2 Tyr, dityrosine, and orthotyrosine, specific molecular fingerprints for distinct oxidative pathways upregulated in atheroma, were determined by mass spectrometry. In parallel, alterations in lipoproteins and C-reactive protein were determined. Statin therapy caused significant reductions in chlorotyrosine, NO 2 Tyr, and dityrosine (30%, 25%, and 32%, respectively; PϽ0.02 each) that were similar in magnitude to reductions in total cholesterol and apolipoprotein B-100 (25% and 29%, PϽ0.001 each). Nonsignificant decreases in orthotyrosine and C-reactive protein levels were observed (9% and 11%, respectively; PϾ0.10 each). Statin-induced reductions in oxidation markers were independent of decreases in lipids and lipoproteins. Conclusions-Statins

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Section: Discussionsupporting

confidence: 56%

Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory Pathways

et al. 2003

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“…This observation appears sex-specific as this association could not be observed among male subjects. It is most intriguing that these results are corresponding to the associations reported for different diseases such as lung cancer, [12][13][14] esophageal cancer, 15 coronary artery disease, 16 Helicobacter pylori infections 17 and neuro-degenerative disorders, ie Alzheimer's disease 18 and multiple sclerosis. 19 In all these studies, the allelic variant MPO −463A elicited a protective effect with nearly identical odds ratios in the range of 0.3-0.7.…”

Section: Discussionmentioning

confidence: 66%

Gender and smoking-related risk reduction of periodontal disease with variant myeloperoxidase alleles

et al. 2002

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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

106

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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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A functional myeloperoxidase polymorphic variant is associated with coronary artery disease in French-Canadians

Cited by 195 publications

References 7 publications

Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory Pathways

Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory Pathways

Gender and smoking-related risk reduction of periodontal disease with variant myeloperoxidase alleles

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

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