title: Cadmium exposure as measured in blood in relation to macrophage density in symptomatic atherosclerotic plaques from human carotid artery.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.affiliation: 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.
authors.forename: Josefin
authors.initials: J
authors.lastname: Kjelldahl
authors.affiliation: Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg, Sweden. Electronic address: gerd.sallsten@amm.gu.se.
authors.forename: Gerd
authors.initials: G
authors.lastname: Sallsten
authors.affiliation: Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg, Sweden. Electronic address: lars.barregard@amm.gu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Barregard
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: niklas.forsgard@vgregion.se.
authors.forename: Niklas
authors.initials: N
authors.lastname: Forsgard
authors.affiliation: 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.
authors.forename: Klas
authors.initials: K
authors.lastname: Österberg
authors.affiliation: 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.
authors.forename: Lillemor Mattsson
authors.initials: LM
authors.lastname: Hultén
authors.affiliation: 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.
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D050197:Atherosclerosis; D002104:Cadmium / Q000097:blood*; D002340:Carotid Artery Diseases / Q000601:surgery; D017536:Carotid Artery, Common / Q000473:pathology* / Q000601:surgery; D016893:Carotid Stenosis / Q000150:complications; D016894:Endarterectomy, Carotid; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000601:surgery; D012307:Risk Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002104:Cadmium; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018950:Lipopolysaccharide Receptors; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Atherosclerosis; Cadmium; Cardiovascular disease; Carotid artery; Inflammation; Macrophage; Plaque