Copper and zinc concentrations in atherosclerotic plaque and serum in relation to lipid metabolism in patients with carotid atherosclerosis

  • Nebojša M Tasić Dedinje Cardiovascular Institute, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Danijela Tasić DDedinje Cardiovascular Institute, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Petar Otašević Dedinje Cardiovascular Institute, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Mirjana Veselinović Department of Rheumatology, Internal Medicine Clinic, Clinical Centre Kragujevac Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia
  • Vladimir Lj Jakovljević Department of Physiology, Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia
  • Dragan Djurić Institute of Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Djordje Radak Dedinje Cardiovascular Institute, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
DOI: https://doi.org/10.2298/5936
Keywords: zinc, copper, risk factors, arteriosclerosis, carotid stenosis, lipids,

Abstract


Background/Aim. Some oligoelements are now investigated as possibly having a role in atherosclerosis. The aim of this study was to compare the concentrations of copper and zinc in the serum and carotid plaque and parameters of lipid metabolism in patients with different morphology of carotid atherosclerotic plaque. Methods. Carotid endarterectomy due to the significant atherosclerotic stenosis was performed in 91 patients (mean age 64 ± 7). The control group consisted of 27 patients (mean age 58 ± 9), without carotid atherosclerosis. Atheroscletoric plaques were divided into four morphological groups, according to ultrasonic and intraoperative characteristics. Copper and zinc concentrations in the plaque, carotid artery and serum were measured by atomic absorption spectrophotometry. Results. Serum copper concentrations were statistically significantly higher in the patients with hemorrhagic in comparison to those with calcified plaque (1.2 ± 0.9 μmol/L vs 0.7 ± 0.2 μmol/L, respectively; p = 0.021). Zinc concentrations were statistically significantly lower in plaques of the patients with fibrolipid in comparison to those with calcified plaques (22.1 ± 16.3 μg/g vs 38.4 ± 25.8 μg/g, respectively; p = 0.024). A negative significant correlation was found for zinc and triglycerides in the serum in all the patients (r = -0.52, p = 0.025). In the control group we also demonstrated a positive significant correlation for low-density lipoprotein cholesterol and copper in the serum (r = 0.54, p = 0.04). Conclusion. The data obtained in the current study are consistent with the hypothesis that high copper and lower zinc levels may contribute to atherosclerosis and its sequelae as factors in a multifactorial disease. Further studies are necessary in order to conclude whether high concentration of copper and zinc in the serum could be risk factors for atherosclesrosis.

References

Calabresi L, Gomaraschi M, Simonelli S, Bernini F, Franceschini G. HDL and atherosclerosis: Insights from inherited HDL disor-ders. Biochim Biophys Acta 2014; pii: S1388−1981(14)00148-6.

Horsley ET, Burkitt MJ, Jones CM, Patterson RA, Harris LK, Moss NJ, et al. Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions. Arch Biochem Biophys 2007; 465(2): 303−14.

Rajendran R, Ren M, Ning P, Tan KH, Halliwell B, Watt F. Pro-motion of atherogenesis by copper or iron--which is more likely. Biochem Biophys Res Commun 2007; 353(1): 6−10.

Hamilton IM, Gilmore WS, Strain JJ. Marginal copper deficiency and atherosclerosis. Biol Trace Elem Res 2000; 78(1−3): 179−89.

Ghayour-Mobarhan M, Taylor A, Kazemi-Bajestani SM, Lanham-New S, Lamb DJ, Vaidya N, et al. Serum zinc and copper status in dyslipidaemic patients with and without established coronary artery disease. Clin Lab 2008; 54(9−10): 321−9.

Lamb DJ, Avades TY, Ferns GA. Biphasic modulation of ather-osclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit. Int J Exp Pathol 2001; 82(5): 287−94.

Mccord MC, Aizenman E. The role of intracellular zinc release in aging, oxidative stress, and Alzheimer's disease. Front Aging Neurosci 2014; 6: 77. .

Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care 2009; 12(6): 646−52.

Leone N, Courbon D, Ducimetiere P, Zureik M. Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality. Epidemiology 2006; 17(3): 308−14.

Maret W. Molecular aspects of human cellular zinc homeosta-sis: redox control of zinc potentials and zinc signals. Biometals 2009; 22(1): 149−57.

Beletsky VY, Kelley RE, Fowler M, Phifer T. Ultrasound densito-metric analysis of carotid plaque composition. Pathoanatomic correlation. Stroke 1996; 27(12): 2173−7.

Stadler N, Heeneman S, Vöö S, Stanley N, Giles GI, Gang BP, et al. Reduced metal ion concentrations in atherosclerotic plaques from subjects with type 2 diabetes mellitus. Atherosclerosis 2012; 222(2): 512−8.

Stadler N, Lindner RA, Davies MJ. Direct detection and quanti-fication of transition metal ions in human atherosclerotic plaques: evidence for the presence of elevated levels of iron and copper. Arterioscler Thromb Vasc Biol 2004; 24(5): 949−54.

Islamoglu Y, Evliyaoglu O, Tekbas E, Cil H, Elbey MA, Atilgan Z, et al. The relationship between serum levels of Zn and Cu and severity of coronary atherosclerosis. Biol Trace Elem Res 2011; 144(1−3): 436−44.

Burkitt MJ. A critical overview of the chemistry of copper-dependent low density lipoprotein oxidation: roles of lipid hy-droperoxides, alpha-tocopherol, thiols, and ceruloplasmin. Arch Biochem Biophys 2001; 394(1): 117−35.

Kazemi-Bajestani SM, Ghayour-Mobarhan M, Ebrahimi M, Moohebati M, Esmaeili HA, Parizadeh MR, et al. Serum copper and zinc concentrations are lower in Iranian patients with angio-graphically defined coronary artery disease than in subjects with a normal angiogram. J Trace Elem Med Biol 2007; 21(1): 22−8.

Nourmohammadi I, Nazem N, Ehsani-Zenuz A, Moaveni A. Serum levels of Zn, Cu, Cr and Ni in Iranian subjects with atherosclerosis. Arch Irn Med 2001; 4(1): 21−4.

Díaz Romero C, Henríquez Sanchez P, López Blanco F, Rodríguez Rodríguez E, Serra Majem L. Serum copper and zinc concentra-tions in a representative sample of the Canarian population. J Trace Elem Med Biol 2002; 16(2): 75−81.

Alissa EM, Bahjri SM, Ahmed WH, Al-Ama N, Ferns GA. Trace element status in Saudi patients with established atherosclero-sis. J Trace Elem Med Biol 2006; 20(2): 105−14.

Radak D, Cvetković Z, Tasić N, Petrović B, Lacković V, Djordjević-Denić G. The content of copper and zinc in human ulcerated carotid plaque. Srp Arh Celok Lek 2004; 132(3−4): 80−4. (Serbian)

Ghayour-Mobarhan M, Taylor A, New SA, Lamb DJ, Ferns GA. Determinants of serum copper, zinc and selenium in healthy subjects. Ann Clin Biochem 2005; 42(Pt 5): 364−75.

Iskra M, Majewski W, Piorunska-Stolzmann M. Modifications of magnesium and copper concentrations in serum and arterial wall of patients with vascular diseases related to aging, athero-sclerosis and aortic aneurysm. Magnes Res 2002; 15(3−4): 279−85.

Stadler N, Stanley N, Heeneman S, Vacata V, Daemen MJ, Bannon PG, et al.. Accumulation of zinc in human atherosclerotic le-sions correlates with calcium levels but does not protect against protein oxidation. Arterioscler Thromb Vasc Biol 2008; 28(5): 1024−30.

Allen-Redpath K, Ou O, Beattie JH, Kwun IS, Feldmann J, Nixon GF. Marginal dietary zinc deficiency in vivo induces vascular smooth muscle cell apoptosis in large arteries. Cardiovasc Res 2013; 99(3): 525−34.

Togay-Isikay C, Kim J, Betterman K, Andrews C, Meads D, Tesh P, et al. Carotid artery tortuosity, kinking, coiling: stroke risk factor, marker, or curiosity?. Acta Neurol Belg 2005; 105(2): 68−72.

Kawamoto R, Oka Y, Tomita H, Kodama A. Non-HDL choles-terol as a predictor of carotid atherosclerosis in the elderly. J Atheroscler Thromb 2005; 12(3): 143−8.

Johnsen SH, Mathiesen EB, Fosse E, Joakimsen O, Stensland-Bugge E, Njølstad I, et al. Elevated high-density lipoprotein cholesterol levels are protective against plaque progression: a follow-up study of 1952 persons with carotid atherosclerosis the Tromsø study. Circulation 2005; 112(4): 498−504.

Lopes PA, Santos MC, Vicente L, Rodrigues MO, Pavão ML, Nève J, et al. Trace element status (Se, Cu, Zn) in healthy Portuguese subjects of Lisbon population: a reference study. Biol Trace Elem Res 2004; 101(1): 1−17.

Neggers YH, Bindon JR, Dressler WW. The relationship between zinc and copper status and lipid levels in African-Americans. Biol Trace Elem Res 2001; 79(1): 1−13.

Ghayour-Mobarhan M, Shapouri-Moghaddam A, Azimi-Nezhad M, Esmaeili H, Parizadeh SM, Safarian M, Ferns GA. The relation-ship between established coronary risk factors and serum copper and zinc concentrations in a large Persian cohort. J Trace Elem Med Biol 2009; 23(3): 167−75.

Published
2015/11/02
Issue
Vol. 72 No. 9 (2015)
Section
Original Paper