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

Abstract

Objective-Oxidized lipids and proteins, as well as 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. A therosclerosis is a multifactorial disease to which many factors contribute; defining the role of each of these has proved to be problematic. Oxidation, and in particular that of low-density lipoproteins (LDL), has been linked to disease development, 1 although the significance of this process has not been fully established (reviewed 2 ). Previous studies have variously implicated lipoxygenase, peroxynitrite, myeloperoxidase, oxygen radicals, and metal-ions in lesion oxidation (reviewed 2 ). In the case of metal ions, a correlation between iron accumulation and the extent of protein (but not lipid) oxidation has been reported for human lesions. 3 Cholesterol ester and cholesterol accumulation also correlate positively with iron, suggesting that these processes are interlinked. 3,4 These data are consistent with some, but not all, epidemiological studies on the potential links between iron and cardiovascular disease. [5][6][7][8] Zinc ions have been reported to modulate oxidant damage via the displacement of iron and copper from oxidationsensitive sites on erythrocyte membranes, 9 LDL, 10 or liposomes. 11 Epidemiological data indicate that elevated serum zinc levels may be protective against disease. 12 Serum or plasma measurements of zinc in people with established atherosclerosis indicate that low zinc levels are associated with increased disease 13,14 and a postmortem study has reported lower tissue levels of zinc in the abdominal aorta of patients who died of heart disease compared to other causes. 15 In contrast, zinc supplementation of the human diet does not affect the susceptibility of LDL to oxidation ex vivo 16,17 or the concentrations of LDL-cholesterol, total cholesterol, or triglycerides, but has an adverse effect on high-density lipoprotein levels, suggesting that high serum zinc levels may promote disease. 17 Elevated zinc may stimulate the formation of oxidants and inhibit protective enzymes in some cells. 18 Atherosclerotic lesions of cholesterol-fed rabbits contain elevated levels of iron and reduced levels of zinc. 19 -21 Zinc supplementation, via dietary feeding, reduced lesion area despite insignificant changes in lesion zinc concentrations; these changes were ascribed to a displacement of iron by zinc. 20 Zinc supplement...

Relationship between the Levels of MMP-9, TIMP-1, and Zinc in Biological Samples of Patients with Carotid Atherosclerosis

“…Existing data are contradictory regarding the negative or protective effects of zinc in the development of atherosclerosis [22][23][24]. In study of Stadler et al [25], elevated levels of zinc (about 6-fold) were detected in advanced lesions compared to healthy tissue or early lesions. They found the highly-significant positive correlations between zinc and calcium in samples of carotid endarterectomy (r=0.895; P=0.0001).…”

Iron concentrations in atherosclerotic plaque and serum in patients with carotid atherosclerosis

“…The data obtained from these groups were compared to control subjects without significant atherosclerotic changes in carotid artery. Previous studies have reported that advanced atherosclerotic lesions have higher metal ion levels than initial lesions or healthy tissue (11,21,22).…”

Associations of Biomarkers of Atherosclerotic Plaques Instability (MMP-9, TIMP-1) and Zinc Levels in Carotid Atherosclerosis

“…[18] объясняли повышение уровня цинка как защитный эффект при атеросклерозе. Так, цинк может участвовать в механизме повышения стабильности АСБ, путем связывания с компонентами матрикса.…”