Cadmium is a novel and independent risk factor for early atherosclerosis mechanisms and in vivo relevance

Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1392-8. doi: 10.1161/ATVBAHA.109.190082. Epub 2009 Jun 25.


Objective: Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of atherosclerosis.

Methods and results: In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters (ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.6[1.1.-2.3], P=0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm(2), P<0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies.

Conclusions: Our research suggests Cd has promoting effects on early human and murine atherosclerosis, which were partly offset by high Zn concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / chemically induced*
  • Atherosclerosis / pathology
  • Biomarkers / blood
  • Cadmium / adverse effects*
  • Cadmium / blood
  • Cadmium Chloride / toxicity
  • Capillary Permeability / drug effects
  • Carotid Artery Diseases / chemically induced*
  • Carotid Artery Diseases / pathology
  • Cell Death
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chlorides / pharmacology
  • DNA Breaks
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Environmental Pollutants / adverse effects*
  • Environmental Pollutants / blood
  • Environmental Pollutants / toxicity
  • Female
  • Humans
  • Lipid Metabolism / drug effects
  • Logistic Models
  • Mice
  • Mice, Knockout
  • Odds Ratio
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Young Adult
  • Zinc Compounds / pharmacology
  • bcl-X Protein / metabolism


  • Apolipoproteins E
  • Bcl2l1 protein, mouse
  • Biomarkers
  • Chlorides
  • Environmental Pollutants
  • Zinc Compounds
  • bcl-X Protein
  • Cadmium
  • zinc chloride
  • Cadmium Chloride