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


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.
Messner
Barbara
B
Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Innsbruck Medical University, Austria.
Knoflach
Michael
M
Seubert
Andreas
A
Ritsch
Andreas
A
Pfaller
Kristian
K
Henderson
Blair
B
Shen
Ying H
YH
Zeller
Iris
I
Willeit
Johann
J
Laufer
Günther
G
Wick
Georg
G
Kiechl
Stefan
S
Bernhard
David
D
D000293:Adolescent; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002104:Cadmium / Q000009:adverse effects* / Q000097:blood; D019256:Cadmium Chloride / Q000633:toxicity; D002199:Capillary Permeability / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000139:chemically induced* / Q000473:pathology; D016923:Cell Death; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D053960:DNA Breaks; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000097:blood / Q000633:toxicity; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D016015:Logistic Models; D051379:Mice; D018345:Mice, Knockout; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult; D017967:Zinc Compounds / Q000494:pharmacology; D051020:bcl-X Protein / Q000378:metabolism
D001057:Apolipoproteins E; C494812:Bcl2l1 protein, mouse; D015415:Biomarkers; D002712:Chlorides; D004785:Environmental Pollutants; D017967:Zinc Compounds; D051020:bcl-X Protein; D002104:Cadmium; C016837:zinc chloride; D019256:Cadmium Chloride