Marginal Copper Deficiency and Atherosclerosis

Hamilton, Iona M. J.; Gilmore, William S.; Strain, J. J.

doi:10.1385/bter:78:1-3:179

Cited by 50 publications

(39 citation statements)

References 39 publications

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“…Finally, the observed depletion of zinc due to MT sequestration (14,49), associated with copper and magnesium deficiency and iron overload, is in line with previous studies indicating the role of metal dyshomeostasis in atherosclerosis development (6,(50)(51)(52). Low magnesium concentration has been linked to increased rate of cerebrovascular events (53), copper and zinc decrease in ulcerated plaques can promote atheroma destabilization (2) and, as for iron, an overload of this element leads to higher production of reactive oxygen species with subsequent atherosclerosis progression or cardiovascular diseases (12).…”

Section: Discussionsupporting

confidence: 89%

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Giacconi

Muti

Malavolta

et al. 2007

Mol Med

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Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C-carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C-carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.

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Section: Discussionsupporting

confidence: 89%

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Giacconi

Muti

Malavolta

et al. 2007

Mol Med

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“…With regard to Zn, it is not only involved in the activities of about 100 enzymes, e.g., RNA polymerase, carbonic anhydrase. Also Zn is present in antioxidant enzymes, for example, Cu-Zn superoxide dismutase [26,38]. In addition, Zn maintains the physiological values of metallothioneins, which are also antioxidants.…”

Section: Discussionmentioning

confidence: 99%

Trace Elements in Fingernails of Healthy Chinese Centenarians

Zou

et al. 2011

Biol Trace Elem Res

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Trace element concentrations in body tissues of healthy centenarians have not been widely analyzed, yet they can be used as reference data leading to improved assessment of the aging process and monitoring of the micronutrient status of this age group. The present study sought to assess trace element concentrations and behaviors in the fingernails of healthy Chinese centenarians. The effects of gender on element concentrations, which also play an important role in determining the lifespan, were also investigated. Trace elements (Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Se, Sr, and Zn) in the fingernails of 78 healthy Chinese centenarians were determined by inductively coupled plasma mass spectrometry. The overall reference values obtained in milligram per kilogram are as follows: Ba, 5.10; Cd, 0.031; Co, 0.101; Cr, 0.82; Cu, 3.71; Fe, 154.35; Li, 0.31; Mn, 3.09; Mo, 0.040; Ni, 0.95; Pb, 1.86; Se, 0.44; Sr, 6.20; and Zn, 147.96. Data analysis showed that only Cr and Se concentrations show a normal distribution, and no significant difference between male and female groups was found for any element except Cr. Result also revealed that sufficient Se, Co, and Zn as well as lower or lack of exposure to Cr contribute positively to the lifespan of centenarians. The results suggest that regulating in vivo contents of trace elements, especially Se, Co, and Zn, is reasonable to intervene with geriatric diseases.

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“…Also, in apolipoprotein E Ϫ/Ϫ mice, iron overload decreases lesion size despite detectable increases in hepatic concentrations of markers of oxidative events in the liver (485). Similarly, dietary supplementation with copper decreases atherosclerosis in cholesterol-fed rabbits (516), while copper deficiency increases atherosclerosis in C57B mice (354). Together, these results indicate that iron and copper are not likely important catalysts for oxidation events leading to atherosclerosis and that studies using free transition metals such as Cu(II) to oxidize LDL in vitro may not be meaningful biologically.…”

Section: Putative Oxidants Involvedmentioning

confidence: 99%

Role of Oxidative Modifications in Atherosclerosis

Stocker¹,

Keaney²

2004

Physiological Reviews

2,242

1,756

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This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an “oxidative response to inflammation” model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.

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Marginal Copper Deficiency and Atherosclerosis

Cited by 50 publications

References 39 publications

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Trace Elements in Fingernails of Healthy Chinese Centenarians

Role of Oxidative Modifications in Atherosclerosis

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