Abstract
Genetic factors that predispose to hypertension may contribute to element disturbances observed in hypertensive patients. We tested the hypothesis that the deletion allele of the angiotensin-converting enzyme (ACE) gene is associated with element imbalances in hypertension. The concentrations of elements in genetically predisposed to hypertension rats (SHRs) and their controls (WKY rats) were also examined. ICP-MS was used for elemental analysis of human hair and animal fur. Genotyping was performed by PCR. We also measured micronuclei frequency and distribution of peripheral blood leukocytes in cell cycle phases by flow cytometry and studied the correlations of these parameters with element contents. In general, the tendency for higher levels of toxic and lower levels of essential elements is observed in hypertension, specifically in patients carrying the D allele. Hypertensive men had significantly higher Be, V, Cr, As, Mo, Ag, Sb, and Na levels and lower Ca, Zn, Ba, and U levels compared with control subjects; the differences were not significant for Mg, Al, K, Mn, Fe, Co, Ni, Cu, Se, Cd, Tl, Pb, and Th. The D allele was associated with higher Be, Mo, and Th levels and lower Zn, Se, and Tl levels. The concentrations of Ca, Co, Mo and U were higher in SHR than those in the WKY rats. Mo, an antagonist of Cu, positively correlated with the S-phase cells, and Cu positively correlated with micronuclei frequency. The results suggest an involvement of the ACE I/D polymorphism in element imbalances in hypertension and attract attention to the possible significant role of genetic factors in Mo accumulation.
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References
A global brief on Hypertension. World Health Organisation (2013) http://ish-world.com/downloads/pdf/global_brief_hypertension.pdf. Accessed 25 December 2016
Lim SS, Vos T, Flaxman AD et al (2012) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2224–2260. doi:10.1016/S0140-6736(12)61766-8
Ketonen J, Merasto S, Paakkari I, Mervaala EM (2005) High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E-deficient mice. Blood Press 4(6):373–382. doi:10.1080/08037050500383687
Tubeck S (2006) Role of trace elements in primary arterial hypertension: is mineral water style or prophylaxis? Biol Trace Elem Res 114:1–5. doi:10.1385/BTER:114:1:1
Goch A (2005) Concentration of elements in plasma of patients with essential hypertension. Pol Arch Med Wewn 114(4):947–952
Afridi HI, Kazi TG, Talpur FN, Kazi A, Arain SS, Arain SA, Brahman KD, Panhwar AH, Naeemullah SM, Ali J (2014a) Interaction between essential elements selenium and zinc with cadmium and mercury in samples from hypertensive patients. Biol Trace Elem Res 160(2):185–196. doi:10.1007/s12011-014-0048-y
Gonzalez-Munoz MJ, Sanchez-Muniz FJ, Rodenas S, Sevillano MI, Marin MTL, Bastida S (2010) Differences in metal and metalloid content in the hair of normo- and hypertensive postmenopausal women. Hypertens Res 33:219–224. doi:10.1038/hr.2009.221
Gouaref I, Bellahsene Z, Zekri S, Alamir B, Koceir EA (2016) The link between trace elements and metabolic syndrome/oxidative stress in essential hypertension with or without type 2 diabetes. Ann Biol Clin (Paris) 74(2):233–243. doi:10.1684/abc.2016.1126
Von Haehling S, Jankowska EA, van Veldhuisen DJ, Ponikowski P, Anker SD (2015) Iron deficiency and cardiovascular disease. Nat Rev Cardiol 12(11):659–669. doi:10.1038/nrcardio.2015.109
Tomita H (1990) Trace elements in clinical medicine proceedings of the second meeting of the International Society for Trace Element Research in Humans (ISTERH) August 28–September 1, 1989. Springer-Verlag, Tokyo
Hitomi H, Kiyomoto H, Nishiyama A (2007) Angiotensin II and oxidative stress. Curr Opin Cardiol 22(4):311–315. doi:10.1097/HCO.0b013e3281532b53
Rigat B, Hubert C, Corvo P, Soubrier F (1992) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucl Acids Res 20(6):1433
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86(4):1343–1346. doi:10.1172/JCI114844
Lachurié ML, Azizi M, Guyene TT, Alhenc-Gelas F, Ménard J (1995) Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. Circulation 91(12):2933–2942. doi:10.1161/01.CIR.91.12.2933
O'Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, Myers RH, Levy D (1998) Evidence for association and genetic linkage of the angiotensinconverting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 97(18):1766–1772. doi:10.1161/01.CIR.97.18.1766
Krishnana R, Sekara D, Karunanithyb S, Subramaniumb S (2016) Association of angiotensin converting enzyme gene insertion/deletion polymorphism with essential hypertension in south Indian population. Genes & Diseases 3(2):159–163
Mao S, Li C (2015) Hypotensive and angiotensin-converting enzyme inhibitory activities of eisenia fetida extract in spontaneously hypertensive rats. Evid Based Complement Alternat Med 2015:1–7. doi:10.1155/2015/349721
Zimmer J, Hawlitschek C, Rabald S, Hagendorff A, Zimmer HG, Rassler B (2015) Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: echocardiographic studies. Hypertens Res 38(11):716–722. doi:10.1038/hr.2015.68
Alissa EM, Ferns GA (2011) Heavy metal poisoning and cardiovascular disease. J Toxicol 2011:870125. doi:10.1155/2011/870125
Wołowiec P, Michalak I, Chojnacka K, Mikulewicz M (2013) Hair analysis in health assessment. Clin Chim Acta 419:139–171. doi:10.1016/j.cca.2013.02.001
Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L, Neal B, Rodgers A, Ni Mhurchu C, Clark T (1999) 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization. Clin Exp Hypertens 21(5–6):1009–1060. doi:10.3109/10641969909061028
Hedayati SS, Minhajuddin AT, Ijaz A, Moe OW, Elsayed EF, Reilly RF, Huang CL (2012) Association of Urinary Sodium/potassium ratio with blood pressure: sex and racial differences. Clin J Am Soc Nephrol 7(2):315–322. doi:10.2215/CJN.02060311
Biino G, Parati G, Concas MP, Adamo M, Angius A, Vaccargiu S, Pirastu M (2013) Environmental and genetic contribution to hypertension prevalence: data from an epidemiological survey on Sardinian genetic isolates. PLoS One 8(3):e59612. doi:10.1371/journal.pone.0059612
Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW, Parry J, Norppa H, Eastmond DA, Tucker JD, Thomas P (2011) Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 26(1):125–132. doi:10.1093/mutage/geq052
Bartek J, Lukas C, Lukas J (2004) Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 5(10):792–804. doi:10.1038/nrm1493
Panhwar AH, Kazi TG, Afridi HI, Talpur FN, Arain S, Kazi N (2014) Distribution of potassium, calcium, magnesium, and sodium levels in biological samples of Pakistani hypertensive patients and control subjects. Clin Lab 60(3):463–474
McCarron DA, Morris CD, Henry HJ, Stanton JL (1984) Blood pressure and nutrient intake in the United States. Science 224:1392–1398
Shiue I (2014) Higher urinary heavy metal, phthalate, and arsenic but not parabens concentrations in people with high blood pressure, U.S. NHANES, 2011–2012. Int J Environ Res Public Health 11(6):5989–5999. doi:10.3390/ijerph110605989
Afridi HI, Kazi TG, Talpur FN, Arain S, Arain SS, Kazi N, Panhwar AH (2014b) Distribution of arsenic, cadmium, lead, and nickel levels in biological samples of Pakistani hypertensive patients and control subjects. Clin Lab 60(8):1309–1318
Sun L, Wang X, Yao H, Li W, Son YO, Luo J, Liu J, Zhang Z (2012) Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells. J Environ Pathol Toxicol Oncol 31(2):95–107
Zhang M, Luo J, Zhang C, Cao H, Xia B, Hu G (2016) Alterations in antioxidant function and cell apoptosis in spleens of duck exposed to molybdenum or/and cadmium. The Korean Society of Veterinary Science. http://www.vetsci.org/journal/view.html?uid=1127&vmd=Full. Accessed 14 March 2017
Kumar A, Mishra P, Ghosh S, Sharma P, Ali M, Pandey BN, Mishra KP (2008) Thorium-induced oxidative stress mediated toxicity in mice and its abrogation by diethylenetriamine pentaacetate. Int J Radiat Biol 84(4):337–349. doi:10.1080/09553000801983133
Solenkova NV, Newman JD, Berger JS, Thurston G, Hochman JS, Lamas GA (2014) Metal pollutants and cardiovascular disease: mechanisms and consequences of exposure. Am Heart J 168(6):812–822. doi:10.1016/j.ahj.2014.07.007
Sauk JJ, Somerman MJ (1991) Physiology of bone: mineral compartment proteins as candidates for environmental perturbation by lead. Environ Health Perspect 91:9–16
Andrews GK (2000) Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol 59(1):95–104
Lahera V, Cachofeiro V, de Las HN (2011) Interplay of hypertension, inflammation, and angiotensin II. Am J Hypertens 24(10):1059. doi:10.1038/ajh.2011.142
Mak IT, Landgraf KM, Chmielinska JJ, Weglicki WB (2012) Angiotensin II promotes iron accumulation and depresses PGI2 and NO synthesis in endothelial cells: effects of losartan and propranolol analogs. Can J Physiol Pharmacol 90(10):1413–1418. doi:10.1139/y2012-104
Degani H, Lenkinski RE (1980) Ionophoric properties of angiotensin II peptides. Nuclear magnetic resonance kinetic studies of the hormone-mediated transport of manganese ions across phosphatidylcholine bilayers. Biochemistry 19(15):3430–3434
Ekmekci OB, Donma O, Tunckale A (2003) Angiotensin-converting enzyme and metals in untreated essential hypertension. Biol Trace Elem Res 95(3):203–210. doi:10.1385/BTER:95:3:203
Lau K, Langman CB, Gafter U, Dudeja PK, Brasitus TA (1986) Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity. J Clin Invest 78(4):1083–1090. doi:10.1172/JCI112664
Shiue I, Hristova K (2014) Higher urinary heavy metal, phthalate and arsenic concentrations accounted for 3-19% of the population attributable risk for high blood pressure: US NHANES, 2009-2012. Hypertens Res 37(12):1075–1081. doi:10.1038/hr.2014.121
Rotter I, Kosik-Bogacka D, Dołęgowska B, Safranow K, Lubkowska A, Laszczyńska M (2015) Relationship between the concentrations of heavy metals and bioelements in aging men with metabolic syndrome. Int J Environ Res Public Health 12(4):3944–3961. doi:10.3390/ijerph120403944
Brewer GJ, Dick RD, Grover DK, LeClaire V, Tseng M, Wicha M, Pienta K, Redman BG, Jahan T, Sondak VK, Strawderman M, LeCarpentier G, Merajver SD (2000) Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: phase I study. Clin Cancer Res 6(1):1–10
Humar R, Zimmerli L, Battegay E (2009) Angiogenesis and hypertension: an update. J Hum Hypertens 23:773–782. doi:10.1038/jhh.2009.63
Picco SJ, Abba MC, Mattioli GA, Fazzio LE, Rosa D, De Luca JC, Dulout FN (2004) Association between copper deficiency and DNA damage in cattle. Mutagenesis 19(6):453–456. doi:10.1093/mutage/geh056
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Pavlyushchik, O., Afonin, V., Fatykhava, S. et al. Macro- and Microelement Status in Animal and Human Hypertension: the Role of the ACE Gene I/D Polymorphism. Biol Trace Elem Res 180, 110–119 (2017). https://doi.org/10.1007/s12011-017-0990-6
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DOI: https://doi.org/10.1007/s12011-017-0990-6