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Cadmium exposure as measured in blood in relation to macrophage density in symptomatic atherosclerotic plaques from human carotid artery

Journal article
Authors Björn Fagerberg
Josefin Kjelldahl
Gerd Sällsten
Lars Barregård
N. Forsgard
Klas Österberg
Lillemor Mattsson Hultén
Göran Bergström
Published in Atherosclerosis
Volume 249
Pages 209-214
ISSN 0021-9150
Publication year 2016
Published at Wallenberg Laboratory
Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 209-214
Language en
Links dx.doi.org/10.1016/j.atherosclerosi...
Keywords Cadmium, Carotid artery, Cardiovascular disease, Atherosclerosis, Plaque, Macrophage, Inflammation, CARDIOVASCULAR-DISEASE, INFLAMMATION, STABILIZATION, ASSOCIATION, MORTALITY, STROKE, EXPRESSION, DIRECTION, UPSTREAM, LESIONS
Subject categories Molecular medicine (genetics and pathology), Cardiovascular medicine, Environmental medicine

Abstract

Background and Aims: The general population is exposed to cadmium through diet and smoking. Cadmium is pro-atherogenic and pro-inflammatory in experimental and observational studies. Cadmium levels in blood and carotid plaque endarterectomies correlate. Cadmium concentrations are much higher in plaque-areas that most frequently rupture. Here we investigated if blood cadmium concentrations are associated with macrophage density and the accumulation of CD14 as indicator of macrophage activation by lipopolysaccharide (LPS) in endarterectomies from patients with symptomatic carotid plaques. Methods: Endarterectomies from ninety nine patients were fixed in formalin, embedded in paraffin, serially sectioned and stained for assessment of morphology. As predefined, the two section levels with most prevalent plaque rupture were used for further analyses. Macrophages were assessed as area of staining for CD68 (%). Blood cadmium was measured with ICP-MS. Results: The CD68 median [25,75 percentiles] from the average of both sections were higher in cadmium tertile 3 than in tertile 1 (9.8 [4.9,16.1] % and 3.8 (0.6,12.4) %, p = 0.017). This difference remained in a multiple linear regression analysis with 10log meanCD68 as dependent variable and adjustment for sex, age, smoking, statin treatment, index event, time between event and surgery (beta coefficient 0.44 [95% CI 0.05-0.87]. CD14 was not associated with blood cadmium. Conclusions: The results showed that blood cadmium was associated with proinflammatory macrophage density in the sections of carotid plaques with most frequent rupture, previously shown to contain most cadmium. No association between cadmium and LPS-mediated macrophage-activation was found. Cadmium exposure may promote plaque inflammation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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