Increased serum cadmium and strontium levels in young smokers: effects on arterial endothelial cell gene transcription.
OBJECTIVE
Metal constituents of tobacco have long been suspected to contribute to cardiovascular diseases. In this study, we determined the serum concentrations of aluminum, cadmium (Cd), cobalt, copper, iron, manganese, nickel, lead, strontium (Sr), and zinc of young nonsmokers, passive smokers, and smokers.


RESULTS
Cd and Sr were found to be significantly increased in smokers compared with nonsmokers. The effects of these metals on primary arterial endothelial cells were then assessed using microarray technology and real-time polymerase chain reaction (RT-PCR). The data showed that Sr does not interfere with endothelial cell transcription. In contrast, the effects of Cd in amounts delivered to the human body by smoking were dramatic.


CONCLUSIONS
Arterial endothelial cells responded to Cd exposure by massively upregulating metal and oxidant defense genes (metallothioneins) and by downregulating a number of transcription factors. In addition, the mRNA of the intermediate filament protein vimentin, crucial for the maintenance of cellular shape, was reduced. Surprisingly, a number of pro-inflammatory genes were downregulated in response to Cd. The present data suggest that by delivering Cd to the human body, smoking deregulates transcription, exerts stress, and damages the structure of the vascular endothelium; furthermore, in contrast to the effects of cigarette smoke as a whole, Cd seems to possess anti-inflammatory properties.
Bernhard
David
D
Vascular Biology Group, Division Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria. David.Bernhard@i-med.ac.at
Rossmann
Andrea
A
Henderson
Blair
B
Kind
Michaela
M
Seubert
Andreas
A
Wick
Georg
G
D000328:Adult; D000367:Age Factors; D002104:Cadmium / Q000009:adverse effects / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D019216:Metals, Heavy / Q000097:blood; D012907:Smoking / Q000097:blood*; D013324:Strontium / Q000009:adverse effects / Q000097:blood*; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
D019216:Metals, Heavy; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors; D014746:Vimentin; D002104:Cadmium; D008668:Metallothionein; D013324:Strontium