Björn Fagerberg1, Josefin Kjelldahl2, Gerd Sallsten3, Lars Barregard4, Niklas Forsgard5, Klas Österberg6, Lillemor Mattsson Hultén7, Göran Bergström8. 1. Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: bjorn.fagerberg@wlab.gu.se. 2. Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: josefin.kjelldahl@wlab.gu.se. 3. Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg, Sweden. Electronic address: gerd.sallsten@amm.gu.se. 4. Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg, Sweden. Electronic address: lars.barregard@amm.gu.se. 5. Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: niklas.forsgard@vgregion.se. 6. Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: klas.osterberg@vgregion.se. 7. Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: lillemor.mattsson@wlab.gu.se. 8. Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: goran.bergstrom@hjl.gu.se.
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 (10)log 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.
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 (10)log 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.
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