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Direct Detection and Quantification of Transition Metal Ions in Human Atherosclerotic Plaques: Evidence for the Presence of Elevated Levels of Iron and Copper
Abstract
Objective—The involvement of transition metals in atherosclerosis is controversial. Some epidemiological studies have reported a relationship between iron (Fe) and cardiovascular disease, whereas others have not. Experimental studies have reported elevated levels of iron and copper (Cu) in diseased human arteries but have often used methods that release metal ions from proteins. Methods and Results—In this study, we have used the minimally invasive technique of electron paramagnetic resonance (EPR) spectroscopy and inductively coupled plasma mass spectroscopy (ICPMS) to quantify iron and copper in ex vivo healthy human arteries and carotid lesions. The EPR spectra detected are characteristic of nonheme Fe(III) complexes. Statistically elevated levels of iron were detected in the intima of lesions compared with healthy controls (0.370 versus 0.022 nmol/mg tissue for EPR, 0.525 versus 0.168 nmol/mg tissue by ICPMS,P<0.05 in each cases). Elevated levels of copper were also detected (7.51 versus 2.01 pmol/mg tissue, lesion versus healthy control, respectively,P<0.05). Iron levels did not correlate with the gender or age of the donor, or tissue protein or calcium levels, but cholesterol levels correlated positively with iron accumulation, as measured by EPR. Conclusions—These data support the hypothesis that iron accumulates in human lesions and may contribute to disease progression.
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“The identification of iron accumulation in macrophages as the prime event in the complex pathogenesis of CVUs eventually driving persistent inflammation and tissue damage is also of major relevance for other chronic inflammatory disorders with enhanced iron storage in macrophages, like arteriosclerosis, multiple sclerosis, and other neurodegenerative diseases (79-82).”
From An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice (2011) · cites this paper as [80]
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“Iron and oxidised lipids are both found in atherosclerotic lesions [141,765-777]”
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“in one study (Stadler et al. 2004), the EPR-detectable iron (essentially Fe(III)) in atherosclerotic tissue was seventeen times greater than that in the equivalent healthy tissue”
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Metadata
- Authors
- Stadler, N., Lindner, R. A., & Davies, M. J.
- Affiliations
- The Heart Research Institute (AU)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2004-05
- Volume
- 24
- Issue
- 5
- Pages
- 949-954
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2158913228
- Cited by
- 310
- References
- 51
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 11 · 2022: 12 · 2021: 13 · 2020: 13 · 2019: 11 · 2018: 8 · 2017: 10 · 2016: 13 · 2015: 13 · 2014: 13 · 2013: 23 · 2012: 16
- FWCI
- 14.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Medical Research Council
- Australian Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- atherosclerosis, transition metal ions, iron accumulation, copper, carotid plaque, cholesterol, human arteries
- MeSH terms
- Aged, Aged, 80 and over, Aorta, Coronary Artery Bypass, Carotid Arteries, Carotid Artery Diseases, Cholesterol, Copper, Electron Spin Resonance Spectroscopy, Female, Humans, Iron, Male, Mammary Arteries, Middle Aged, Mass Spectrometry, Endarterectomy, Carotid, Radial Artery, Tunica Intima
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