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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:833.)
© 2006 American Heart Association, Inc.

Vascular Biology

Increased Serum Cadmium and Strontium Levels in Young Smokers

Effects on Arterial Endothelial Cell Gene Transcription

David Bernhard; Andrea Rossmann; Blair Henderson; Michaela Kind; Andreas Seubert; Georg Wick

From Vascular Biology Group (D.B., A.R., B.H., M.K., G.W.), Division Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria; Department of Chemistry (A.S.), Philipps-University of Marburg, Marburg, Germany.

Correspondence to David Bernhard, PhD, Vascular Biology Group, Division Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3/4. OG. 6020 Innsbruck, Austria. E-mail David.Bernhard{at}i-med.ac.at

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.

Methods and 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.

Cigarette smoking interferes with metal homeostasis of the human body. In this study, we show that serum cadmium and strontium levels are significantly increased in smokers compared with nonsmokers. Further, we analyze the effects of these metals on primary arterial endothelial cell transcription using microarray technology and real-time polymerase chain reaction.

Key Words: atherosclerosis • cigarette smoking • endothelial • metals • microarray • osteoporosis

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