Login Register Cart 0
Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Selenium, Selenoproteins and 10-year Cardiovascular Risk: Results from the ATTICA Study

Author(s): Paraskevi Detopoulou, Sophia Letsiou, Tzortzis Nomikos, Alexandros Karagiannis, Spiros A. Pergantis, Christos Pitsavos, Demosthenes B. Panagiotakos and Smaragdi Antonopoulou*

Volume 21, Issue 5, 2023

Published on: 10 August, 2023

Page: [346 - 355] Pages: 10

DOI: 10.2174/1570161121666230731142023

Price: $65

Abstract

Background: Selenium (Se) is an essential trace element that is involved in several pathophysiological functions. The relationship of Se with cardiovascular disease remains inconclusive, especially regarding the role of different selenospecies.

Objective: The present study assessed the levels of Se distribution in plasma selenoproteins, namely glutathione peroxidase 3 (GPx3), selenoprotein P (SelP) and selenoalbumin (SeAlb) and total Se in selenoproteins in relation to 10-year cardiovascular risk in the ATTICA prospective study.

Methods: A sub-sample from the ATTICA Study’s database, consisting of 278 subjects (114 women and 164 men) with data on Se and selenoproteins levels, was considered. SeGPx3, SelP, and SeAlb in human plasma were simultaneously determined by high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) at baseline. The duration of the follow-up was 8.74 ±2.36 years (mean± standard deviation) and cardiovascular outcomes were recorded. Cox proportional hazards models were applied with total Se or selenoprotein Se as independent variables adjusted for several covariates.

Results: Total Se in selenoproteins was positively related to 10-year relative risk of cardiovascular disease (Hazard Ratios of 3rd vs 2nd tertile 10.02, 95% CI:1.15, 92.34). Subjects with high Se but low SeGPx3, as identified by discordant percentiles in the distribution of SeGPx3 and Se, had a higher cardiovascular risk.

Conclusion: The differentiated effects of circulating selenoproteins on cardiovascular disease risk in the present study, suggest the importance of redox regulation by specific selenoproteins.

Keywords: Selenium, selenoproteins, GPx3, selenoprotein P, speciation, ATTICA study, cardiovascular disease.

« Previous Next »
Graphical Abstract

[1]
Yang L, Qi M, Du X, et al. Selenium concentration is associated with occurrence and diagnosis of three cardiovascular diseases: A systematic review and meta-analysis. J Trace Elem Med Biol 2022; 70: 126908.
[http://dx.doi.org/10.1016/j.jtemb.2021.126908] [PMID: 34902677]
[2]
Shi Y, Yang W, Tang X, Yan Q, Cai X, Wu F. Keshan disease: A potentially fatal endemic cardiomyopathy in remote mountains of] China. Front Pediatr 2021; 9: 576916.
[http://dx.doi.org/10.3389/fped.2021.576916] [PMID: 33768083]
[3]
Al-Mubarak AA, van der Meer P, Bomer N. Selenium, selenoproteins, and heart failure: Current knowledge and future perspective. Curr Heart Fail Rep 2021; 18(3): 122-31.
[http://dx.doi.org/10.1007/s11897-021-00511-4] [PMID: 33835398]
[4]
Liu H, Xu H, Huang K. Selenium in the prevention of atherosclerosis and its underlying mechanisms. Metallomics 2017; 9(1): 21-37.
[http://dx.doi.org/10.1039/C6MT00195E] [PMID: 28009916]
[5]
Bjørklund G, Shanaida M, Lysiuk R, et al. Selenium: An antioxidant with a critical role in anti-aging. Molecules 2022; 27(19): 6613.
[http://dx.doi.org/10.3390/molecules27196613] [PMID: 36235150]
[6]
Detopoulou P, Demopoulos CA, Antonopoulou S. Micronutrients, phytochemicals and mediterranean diet: A potential protective role against covid-19 through modulation of paf actions and metabolism. Nutrients 2021; 13(2): 462.
[http://dx.doi.org/10.3390/nu13020462] [PMID: 33573169]
[7]
Hariharan S, Dharmaraj S. Selenium and selenoproteins: It’s role in regulation of inflammation. Inflammopharmacology 2020; 28(3): 667-95.
[http://dx.doi.org/10.1007/s10787-020-00690-x] [PMID: 32144521]
[8]
Kryukov GV, Castellano S, Novoselov SV, et al. Characterization of mammalian selenoproteomes. Science 2003; 300(5624): 1439-43.
[http://dx.doi.org/10.1126/science.1083516] [PMID: 12775843]
[9]
Shimada BK, Alfulaij N, Seale LA. The impact of selenium deficiency on cardiovascular function. Int J Mol Sci 2021; 22(19): 10713.
[http://dx.doi.org/10.3390/ijms221910713] [PMID: 34639053]
[10]
Schomburg L, Selenoprotein P. Selenium transport protein, enzyme and biomarker of selenium status. Free Radic Biol Med 2022; 191: 150-63.
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.08.022] [PMID: 36067902]
[11]
Berger MM, Shenkin A, Schweinlin A, et al. ESPEN micronutrient guideline. Clin Nutr 2022; 41(6): 1357-424.
[http://dx.doi.org/10.1016/j.clnu.2022.02.015] [PMID: 35365361]
[12]
Kitabayashi N, Nakao S, Mita Y, et al. Role of selenoprotein P expression in the function of pancreatic β cells: Prevention of ferroptosis-like cell death and stress-induced nascent granule degradation. Free Radic Biol Med 2022; 183: 89-103.
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.03.009] [PMID: 35318102]
[13]
Steinbrenner H, Steinbrenner H, Bilgic E, et al. Selenoprotein P protects endothelial cells from oxidative damage by stimulation of glutathione peroxidase expression and activity. Free Radic Res 2006; 40(9): 936-43.
[http://dx.doi.org/10.1080/10715760600806248] [PMID: 17015273]
[14]
Schrauzer GN. Selenomethionine: A review of its nutritional significance, metabolism and toxicity. J Nutr 2000; 130(7): 1653-6.
[http://dx.doi.org/10.1093/jn/130.7.1653] [PMID: 10867031]
[15]
McClung JP, Roneker CA, Mu W, et al. Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Proc Natl Acad Sci 2004; 101(24): 8852-7.
[http://dx.doi.org/10.1073/pnas.0308096101] [PMID: 15184668]
[16]
Rayman MP. Selenium and human health. Lancet 2012; 379(9822): 1256-68.
[http://dx.doi.org/10.1016/S0140-6736(11)61452-9] [PMID: 22381456]
[17]
Yu R, Wang Z, Ma M, et al. Associations between circulating selenop level and disorders of glucose and lipid metabolism: A meta-analysis. Antioxidants 2022; 11(7): 1263.
[http://dx.doi.org/10.3390/antiox11071263] [PMID: 35883754]
[18]
Panel on dietary antioxidants and related compounds, subcommittee on upper reference levels of nutrients, subcommittee on interpretation and uses of dietary reference intakes. In: Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C: National Academies Press 2000.
[19]
Tan Q, Huang Y, Liu X, et al. A U-shaped relationship between selenium concentrations and all-cause or cardiovascular mortality in patients with hypertension. Front Cardiovasc Med 2021; 8: 671618.
[http://dx.doi.org/10.3389/fcvm.2021.671618] [PMID: 34395551]
[20]
Salonen J, Alfthan G, Huttunen J, Pikkarainen J, Puska P. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982; 320(8291): 175-9.
[http://dx.doi.org/10.1016/S0140-6736(82)91028-5] [PMID: 6123886]
[21]
Pitsavos C, Panagiotakos DB, Chrysohoou C, Stefanadis C. Epidemiology of cardiovascular risk factors in Greece: Aims, design and baseline characteristics of the ATTICA study. BMC Public Health 2003; 3(1): 32.
[http://dx.doi.org/10.1186/1471-2458-3-32] [PMID: 14567760]
[22]
Panagiotakos DB, Georgousopoulou EN, Pitsavos C, et al. Ten-year (2002–2012) cardiovascular disease incidence and all-cause mortality, in urban Greek population: The ATTICA study. Int J Cardiol 2015; 180: 178-84.
[http://dx.doi.org/10.1016/j.ijcard.2014.11.206] [PMID: 25463360]
[23]
Hallal PC, Victora CG. Reliability and validity of the international physical activity questionnaire (IPAQ). Med Sci Sports Exerc 2004; 36(3): 556.
[http://dx.doi.org/10.1249/01.MSS.0000117161.66394.07] [PMID: 15076800]
[24]
Letsiou S, Nomikos T, Panagiotakos DB, et al. Gender-specific distribution of selenium to serum selenoproteins: Associations with total selenium levels, age, smoking, body mass index, and physical activity. Biofactors 2014; 40(5): 524-35.
[http://dx.doi.org/10.1002/biof.1176] [PMID: 25185791]
[25]
Letsiou S, Lu Y, Nomikos T, et al. High-throughput quantification of selenium in individual serum proteins from a healthy human population using HPLC on-line with isotope dilution inductively coupled plasma-MS. Proteomics 2010; 10(19): 3447-57.
[http://dx.doi.org/10.1002/pmic.200900677] [PMID: 20827730]
[26]
Combs GF Jr. Selenium in global food systems. Br J Nutr 2001; 85(5): 517-47.
[http://dx.doi.org/10.1079/BJN2000280] [PMID: 11348568]
[27]
Santos C, García-Fuentes E, Callejón-Leblic B, et al. Selenium, selenoproteins and selenometabolites in mothers and babies at the time of birth. Br J Nutr 2017; 117(9): 1304-11.
[http://dx.doi.org/10.1017/S0007114517001155] [PMID: 28534447]
[28]
Roman M, Lapolla A, Jitaru P, et al. Plasma selenoproteins concentrations in type 2 diabetes mellitus—a pilot study. Transl Res 2010; 156(4): 242-50.
[http://dx.doi.org/10.1016/j.trsl.2010.07.006] [PMID: 20875901]
[29]
Achouba A, Dumas P, Ouellet N, Lemire M, Ayotte P. Plasma levels of selenium-containing proteins in Inuit adults from Nunavik. Environ Int 2016; 96: 8-15.
[http://dx.doi.org/10.1016/j.envint.2016.08.015] [PMID: 27588697]
[30]
Ballihaut G, Kilpatrick LE, Davis WC. Detection, identification, and quantification of selenoproteins in a candidate human plasma standard reference material. Anal Chem 2011; 83(22): 8667-74.
[http://dx.doi.org/10.1021/ac2021147] [PMID: 22007999]
[31]
Jitaru P, Roman M, Cozzi G, Fisicaro P, Cescon P, Barbante C. Speciation analysis of selenoproteins in human serum by microbore affinity-HPLC hyphenated to ICP-Sector field-MS using a high efficiency sample introduction system. Mikrochim Acta 2009; 166(3-4): 319-27.
[http://dx.doi.org/10.1007/s00604-009-0208-5]
[32]
Hinojosa Reyes L, Marchante-Gayón JM, García Alonso JI, Sanz-Medel A. Quantitative speciation of selenium in human serum by affinity chromatography coupled to post-column isotope dilution analysis ICP-MS. J Anal At Spectrom 2003; 18(10): 1210-6.
[http://dx.doi.org/10.1039/B305455A]
[33]
Combs GF Jr, Watts JC, Jackson MI, et al. Determinants of selenium status in healthy adults. Nutr J 2011; 10(1): 75.
[http://dx.doi.org/10.1186/1475-2891-10-75] [PMID: 21767397]
[34]
Reeves MA, Hoffmann PR. The human selenoproteome: Recent insights into functions and regulation. Cell Mol Life Sci 2009; 66(15): 2457-78.
[http://dx.doi.org/10.1007/s00018-009-0032-4] [PMID: 19399585]
[35]
Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E. Selenium and coronary heart disease: A meta-analysis. Am J Clin Nutr 2006; 84(4): 762-73.
[http://dx.doi.org/10.1093/ajcn/84.4.762] [PMID: 17023702]
[36]
Xiang S, Dai Z, Man C, Fan Y. Circulating selenium and cardiovascular or all-cause mortality in the general population: A meta-analysis. Biol Trace Elem Res 2020; 195(1): 55-62.
[http://dx.doi.org/10.1007/s12011-019-01847-8] [PMID: 31368032]
[37]
Zhao D, Domingo-Relloso A, Tellez-Plaza M, et al. High level of selenium exposure in the strong heart study: A cause for incident cardiovascular disease? Antioxid Redox Signal 2022; 37(13-15): 990-7.
[http://dx.doi.org/10.1089/ars.2022.0029] [PMID: 35350849]
[38]
Hu XF, Stranges S, Chan LHM. Circulating selenium concentration is inversely associated with the prevalence of stroke: Results from the canadian health measures survey and the national health and nutrition examination survey. J Am Heart Assoc 2019; 8(10): e012290.
[http://dx.doi.org/10.1161/JAHA.119.012290] [PMID: 31084244]
[39]
Gutiérrez-Bedmar M, Gil F, Olmedo P, et al. Serum selenium and incident cardiovascular disease in the prevención con dieta mediterránea (PREDIMED) trial: Nested case-control study. J Clin Med 2022; 11(22): 6664.
[http://dx.doi.org/10.3390/jcm11226664] [PMID: 36431140]
[40]
Stranges S, Marshall JR, Trevisan M, et al. Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial. Am J Epidemiol 2006; 163(8): 694-9.
[http://dx.doi.org/10.1093/aje/kwj097] [PMID: 16495471]
[41]
Ju W, Li X, Li Z, et al. The effect of selenium supplementation on coronary heart disease: A systematic review and meta-analysis of randomized controlled trials. J Trace Elem Med Biol 2017; 44: 8-16.
[http://dx.doi.org/10.1016/j.jtemb.2017.04.009] [PMID: 28965605]
[42]
Weekley CM, Harris HH. Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem Soc Rev 2013; 42(23): 8870-94.
[http://dx.doi.org/10.1039/c3cs60272a] [PMID: 24030774]
[43]
Rose AH, Hoffmann P. Selenoproteins and cardiovascular stress. Thromb Haemost 2015; 113(3): 494-504.
[http://dx.doi.org/10.1160/TH14-07-0603] [PMID: 25354851]
[44]
Benstoem C, Goetzenich A, Kraemer S, et al. Selenium and its supplementation in cardiovascular disease--what do we know? Nutrients 2015; 7(5): 3094-118.
[http://dx.doi.org/10.3390/nu7053094] [PMID: 25923656]
[45]
Kelishadi MR, Ashtary-Larky D, Davoodi SH, Clark CCT, Asbaghi O. The effects of selenium supplementation on blood lipids and blood pressure in adults: A systematic review and dose-response meta-analysis of randomized control trials. J Trace Elem Med Biol 2022; 74: 127046.
[http://dx.doi.org/10.1016/j.jtemb.2022.127046] [PMID: 35963054]
[46]
Godos J, Giampieri F, Micek A, et al. Effect of brazil nuts on selenium status, blood lipids, and biomarkers of oxidative stress and inflammation: A systematic review and meta-analysis of randomized clinical trials. Antioxidants 2022; 11(2): 403.
[http://dx.doi.org/10.3390/antiox11020403] [PMID: 35204285]
[47]
Laclaustra M, Navas-Acien A, Stranges S, Ordovas JM, Guallar E. Serum selenium concentrations and hypertension in the US Population. Circ Cardiovasc Qual Outcomes 2009; 2(4): 369-76.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.108.831552] [PMID: 20031863]
[48]
Hercberg S, Bertrais S, Czernichow S, et al. Alterations of the lipid profile after 7.5 years of low-dose antioxidant supplementation in the SU.VI.MAX study. Lipids 2005; 40(4): 335-42.
[http://dx.doi.org/10.1007/s11745-006-1391-3] [PMID: 16032784]
[49]
Stranges S, Navas-Acien A, Rayman MP, Guallar E. Selenium status and cardiometabolic health: State of the evidence. Nutr Metab Cardiovasc Dis 2010; 20(10): 754-60.
[http://dx.doi.org/10.1016/j.numecd.2010.10.001] [PMID: 21094028]
[50]
Tanguy S, Grauzam S, de Leiris J, Boucher F. Impact of dietary selenium intake on cardiac health: Experimental approaches and human studies. Mol Nutr Food Res 2012; 56(7): 1106-21.
[http://dx.doi.org/10.1002/mnfr.201100766] [PMID: 22760983]
[51]
Jenkins DJA, Kitts D, Giovannucci EL, et al. Selenium, antioxidants, cardiovascular disease, and all-cause mortality: A systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2020; 112(6): 1642-52.
[http://dx.doi.org/10.1093/ajcn/nqaa245] [PMID: 33053149]
[52]
Alehagen U, Johansson P, Björnstedt M, Rosén A, Dahlström U. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol 2013; 167(5): 1860-6.
[http://dx.doi.org/10.1016/j.ijcard.2012.04.156] [PMID: 22626835]
[53]
Opstad TB, Alexander J, Aaseth JO, Larsson A, Seljeflot I, Alehagen U. Selenium and coenzyme q10 intervention prevents telomere attrition, with association to reduced cardiovascular mortality—sub-study of a randomized clinical trial. Nutrients 2022; 14(16): 3346.
[http://dx.doi.org/10.3390/nu14163346] [PMID: 36014852]
[54]
Letsiou S, Nomikos T, Panagiotakos D, et al. Dietary habits of Greek adults and serum total selenium concentration: The ATTICA study. Eur J Nutr 2010; 49(8): 465-72.
[http://dx.doi.org/10.1007/s00394-010-0105-z] [PMID: 20386916]
[55]
Bakan N, Taysi S, Yilmaz Ö, et al. Glutathione peroxidase, glutathione reductase, Cu–Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia. Clin Chim Acta 2003; 338(1-2): 143-9.
[http://dx.doi.org/10.1016/j.cccn.2003.08.013] [PMID: 14637279]
[56]
Brigelius-Flohé R, Flohé L. Selenium and redox signaling. Arch Biochem Biophys 2017; 617: 48-59.
[http://dx.doi.org/10.1016/j.abb.2016.08.003] [PMID: 27495740]
[57]
Kurokawa S, Berry MJ. Selenium. Role of the essential metalloid in health. In: Sigel A, Sigel H, Sigel RKO, Eds. Interrelations between Essential Metal Ions and Human Diseases. 499-534.
[http://dx.doi.org/10.1007/978-94-007-7500-8_16]
[58]
Blankenberg S, Rupprecht HJ, Bickel C, et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 2003; 349(17): 1605-13.
[http://dx.doi.org/10.1056/NEJMoa030535] [PMID: 14573732]
[59]
Kok FJ. De BRUIJN AM, Hofman A, Valkenburg HA. Selenium status and chronic disease mortality: Dutch epidemiological findings. Int J Epidemiol 1987; 16(2): 329-32.
[http://dx.doi.org/10.1093/ije/16.2.329] [PMID: 3610463]
[60]
Roshanravan N, Koche Ghazi MK, Ghaffari S, et al. Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status. Nutr Metab Cardiovasc Dis 2022; 32(6): 1528-37.
[http://dx.doi.org/10.1016/j.numecd.2022.02.014] [PMID: 35365371]
[61]
Gharipour M, Ouguerram K, Nazih EH, et al. Effects of selenium supplementation on expression of SEPP1 in mRNA and protein levels in subjects with and without metabolic syndrome suffering from coronary artery disease: Selenegene study a double‐blind randomized controlled trial. J Cell Biochem 2018; 119(10): 8282-9.
[http://dx.doi.org/10.1002/jcb.26844] [PMID: 29932230]
[62]
Müller SM, Dawczynski C, Wiest J, Lorkowski S, Kipp AP, Schwerdtle T. Functional biomarkers for the selenium status in a human nutritional intervention study. Nutrients 2020; 12(3): 676.
[http://dx.doi.org/10.3390/nu12030676] [PMID: 32131476]

Rights & Permissions Print Cite
Article Metrics
40
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy