Reduced metal ion concentrations in atherosclerotic plaques from subjects with type 2 diabetes mellitus

TY - JOUR

T1 - Reduced metal ion concentrations in atherosclerotic plaques from subjects with type 2 diabetes mellitus

AU - Stadler, Nadina

AU - Heeneman, Sylvia

AU - Vöö, Stefan

AU - Stanley, Naomi

AU - Giles, Gregory I

AU - Gang, Bevan P

AU - Croft, Kevin D

AU - Mori, Trevor A

AU - Vacata, Vladimir

AU - Daemen, Mat J A P

AU - Waltenberger, Johannes

AU - Davies, Michael Jonathan

N1 - Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

PY - 2012/6

Y1 - 2012/6

N2 - Aims: Transition metal ions have been implicated in atherosclerosis. The goal of this study was to investigate whether metal ion levels were higher in people with diabetes, in view of their increased risk of aggravated atherosclerosis. Methods and results: Absolute concentrations of iron, copper, zinc and calcium, and products of protein and lipid oxidation were quantified in atherosclerotic lesions from subjects with (T2DM, n=27), without Type 2 diabetes (nonDM, n=22), or hyperglycaemia (HG, n=17). Iron (P<0.05), zinc (P<0.01) and calcium (P=0.01) were lower in T2DM compared to nonDM subjects. Copper levels were comparable. A strong correlation (r=0.618; P<0.001) between EPR-detectable and total iron in nonDM patients was not seen in T2DM. X-ray fluorescence microscopy revealed " hot spots" of iron in both T2DM and nonDM. Calcium and zinc co-localised and levels correlated strongly. F2-isoprostanes (P<0.05) and di-Tyr/Tyr ratio (P<0.025), oxidative damage markers were decreased in T2DM compared to nonDM, or HG. Conclusion: Advanced atherosclerotic lesions from T2DM subjects unexpectedly contained lower levels of transition metal ions, and protein and lipid oxidation products, compared to nonDM and HG. These data do not support the hypothesis that elevated metal ion levels may be a major causative factor in the aggravated atherosclerosis observed in T2DM patients.

AB - Aims: Transition metal ions have been implicated in atherosclerosis. The goal of this study was to investigate whether metal ion levels were higher in people with diabetes, in view of their increased risk of aggravated atherosclerosis. Methods and results: Absolute concentrations of iron, copper, zinc and calcium, and products of protein and lipid oxidation were quantified in atherosclerotic lesions from subjects with (T2DM, n=27), without Type 2 diabetes (nonDM, n=22), or hyperglycaemia (HG, n=17). Iron (P<0.05), zinc (P<0.01) and calcium (P=0.01) were lower in T2DM compared to nonDM subjects. Copper levels were comparable. A strong correlation (r=0.618; P<0.001) between EPR-detectable and total iron in nonDM patients was not seen in T2DM. X-ray fluorescence microscopy revealed " hot spots" of iron in both T2DM and nonDM. Calcium and zinc co-localised and levels correlated strongly. F2-isoprostanes (P<0.05) and di-Tyr/Tyr ratio (P<0.025), oxidative damage markers were decreased in T2DM compared to nonDM, or HG. Conclusion: Advanced atherosclerotic lesions from T2DM subjects unexpectedly contained lower levels of transition metal ions, and protein and lipid oxidation products, compared to nonDM and HG. These data do not support the hypothesis that elevated metal ion levels may be a major causative factor in the aggravated atherosclerosis observed in T2DM patients.

KW - Autopsy

KW - Calcium

KW - Carotid Arteries

KW - Carotid Artery Diseases

KW - Copper

KW - Diabetes Mellitus, Type 2

KW - Diabetic Angiopathies

KW - Down-Regulation

KW - Electron Spin Resonance Spectroscopy

KW - F2-Isoprostanes

KW - Female

KW - Humans

KW - Iron

KW - Lipids

KW - Male

KW - Mass Spectrometry

KW - Metals

KW - Microscopy, Fluorescence

KW - Netherlands

KW - Oxidation-Reduction

KW - Plaque, Atherosclerotic

KW - Zinc

U2 - 10.1016/j.atherosclerosis.2012.03.015

DO - 10.1016/j.atherosclerosis.2012.03.015

M3 - Journal article

C2 - 22521900

SN - 0021-9150

VL - 222

SP - 512

EP - 518

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -