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Published Online
on February 28, 2008

Arteriosclerosis, Thrombosis, and Vascular Biology. 2008
Published online before print February 28, 2008, doi: 10.1161/ATVBAHA.108.162735
A more recent version of this article appeared on May 1, 2008
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Submitted on September 12, 2007
Accepted on February 15, 2008

Accumulation of Zinc in Human Atherosclerotic Lesions Correlates With Calcium Levels but Does Not Protect Against Protein Oxidation

Nadina Stadler ; Naomi Stanley ; Sylvia Heeneman ; Vladimir Vacata ; Mat J.A.P. Daemen ; Paul G. Bannon ; Johannes Waltenberger ; and Michael J. Davies *

From the Heart Research Institute (N. Stadler, N. Stanley, M.J.D.), Sydney, Australia; the Cardiovascular Research Institute Maastricht (CARIM) (N. Stadler, S.H., M.J.A.P.D., J.W.), Maastricht, The Netherlands; Gemeinschaftspraxis für Laboratoriumsmedizin (V.V.), Leverkusen, Germany; and the Baird Institute for Heart and Lung Surgical Research (P.G.B.), Sydney, Australia.

* To whom correspondence should be addressed. E-mail: daviesm{at}hri.org.au.

Objective—Oxidized lipids and proteins, and decreased antioxidant levels, have been detected in human atherosclerotic lesions, with oxidation catalyzed by iron and copper postulated to contribute to lesion development. Zinc has been postulated to displace iron from critical sites and thereby protect against damage. In this study, metal ion and protein oxidation levels were quantified in human carotid and abdominal artery specimens containing early to advanced lesions, to determine whether zinc concentrations correlate inversely with iron levels and protein oxidation.

Methods and Results—Metal ions were quantified by EPR and inductively coupled plasma mass spectroscopy. Native and oxidized protein side-chains were quantified by high-performance liquid chromatography. Elevated levels of zinc ({approx}6-fold) were detected in advanced lesions compared to healthy tissue or early lesions. Zinc did not correlate negatively with iron or copper levels suggesting that zinc does not displace these metal ions. Highly significant positive correlations (P<0.005) were detected between zinc and calcium levels.

Conclusions—Zinc did not correlate with low iron levels and reduced protein oxidation. These data indicate that zinc does not prevent protein oxidation in advanced lesions. The reported protective effect of zinc accumulation is proposed to be associated with lesion calcification.
Key words: atherosclerosis • iron • zinc • protein oxidation • calcium






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