title: Non-toxic cadmium concentrations induce vascular inflammation and promote atherosclerosis.
abstract: BACKGROUND
  Cadmium is a potential new risk factor for early atherosclerosis and cardiovascular diseases in humans, yet pathogenetic mechanisms are still a matter of debate.
  
  
  RESULTS
  In-depth histological analysis of 18 sections taken from 6 cadmium-fed ApoE-/- mice and 12 sections from 5 litter-mates not exposed to cadmium by light and scanning electron microscopy was performed. Cadmium-fed mice showed a marked increase in lesion load (plaque area) and severity as classified according to the American Heart Association vascular lesion grading. All inflammatory markers studied (CD68, CD3, CD25, vascular cell adhesion molecule 1 (VCAM-1), and heat shock protein 60 (Hsp60)) yielded a higher expression in cadmium-fed mice. Statistical difference was achieved for VCAM-1 and Hsp60 (P=0.03 and P=0.02). The shoulder region of atherosclerotic plaques in cadmium-fed mice showed a prominent retraction of endothelial cells on electron microscopy.
  
  
  CONCLUSIONS
  Our data indicate that cadmium exposure amplifies the development of vessel pathology in atherosclerosis susceptible ApoE-/- mice and suggests upregulation of VCAM-1 and Hsp60 and endothelial leakage as potential pathomechanisms.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Michael.Knofach@i-med.ac.at
authors.forename: Michael
authors.initials: M
authors.lastname: Knoflach
authors.forename: Barbera
authors.initials: B
authors.lastname: Messner
authors.forename: Ying H
authors.initials: YH
authors.lastname: Shen
authors.forename: Sandra
authors.initials: S
authors.lastname: Frotschnig
authors.forename: Guanghui
authors.initials: G
authors.lastname: Liu
authors.forename: Kristian
authors.initials: K
authors.lastname: Pfaller
authors.forename: Xingli
authors.initials: X
authors.lastname: Wang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Matosevic
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.forename: Günther
authors.initials: G
authors.lastname: Laufer
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000139:chemically induced*; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D018834:Chaperonin 60 / Q000032:analysis; D004730:Endothelium, Vascular / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000473:pathology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D014657:Vasculitis / Q000139:chemically induced*
chemical_list: D001057:Apolipoproteins E; D018834:Chaperonin 60; D019010:Vascular Cell Adhesion Molecule-1; D002104:Cadmium