Myeloperoxidase/high-density lipoprotein cholesterol ratio in patients with arterial hypertension and chronic coronary heart disease

Abstract

BACKGROUND: Myeloperoxidase (MPO), the enzyme of leukocytes, catalyzes the production of reactive halogen species, which can modify the structure of lipoproteins. Chlorination and nitration of tyrosine residues in apolipoprotein A-1 lead to the formation of dysfunctional high-density lipoproteins (HDL-p), thus blocking the reverse cholesterol transport. Low level of high-density lipoprotein cholesterol (HDL-C) is associated with exacerbation of coronary heart disease, but the prognostic value of this index is not fully assessed.

AIM: The aim of this study was to examine a possible contribution of MPO to the atherosclerotic plaque development (the stable growth or the erosion and rupture) via the modification of HDL-p. That is to say we investigated the diagnostic values of measuring the total MPO (MPO-T), the active MPO (MPO-A) and the MPO/HDL-С relation in patients with hypertension and various forms of chronic coronary heart disease.

MATERIALS AND METHODS: The cohort under study included 44 patients with arterial hypertension and chronic coronary heart disease. All patients were divided into three groups according to the diagnosis: arterial hypertension without coronary heart disease (Group I, n = 20); arterial hypertension and the initially stable chronic coronary heart disease without acute complications in the anamnesis (Group II, n = 14); arterial hypertension and myocardial infarction (acute coronary syndrome) in the anamnesis (Group III, n = 10). The enzyme-linked immunosorbent assay (ELISA) for MPO-T and specific immuno-extraction followed by enzymatic detection (SIEFED) by fluorogenic substrate for MPO-A were applied. After that the ratio MPO-T/HDL-C or MPO-A/HDL-C was calculated.

RESULTS: The MPO-A and MPO-A/HDL-C ratio were significantly increased in the group III of patients with old myocardial infarction as compared with the patients of group II who had the initially stable coronary heart disease (p = 0.009 and p = 0.003, respectively). Besides, the level of HDL-C in the group III was significantly reduced (p = 0.013). Our measurements revealed the negative correlation between MPO-A and HDL-C concentrations (r = –0.31; p < 0.05), which is in line with the presumption of the study accomplished. Surprisingly, the correlation between MPO-T/HDL-C ratio and that MPO-A/HDL-C was stronger (r = 0.72; p < 0.05), than between MPO-T and MPO-A (r = 0.36; p < 0.05).

CONCLUSIONS: Our study demonstrates the importance of assessing MPO-T and MPO-A plasma concentrations and of calculating the ratio MPO/HDL-C as promising biomarkers in the complicated cases of chronic coronary heart disease. MPO-A and MPO-A/HDL-C values were elevated in the patients with old myocardial infarction, while the concentration of HDL-C remained decreased upon the transition from the acute to chronic phase of the disease.

Keywords

myeloperoxidase / high-density lipoproteins / coronary heart disease / ELISA / SIEFED

References

[1] Panasenko OM, Gorudko IV, Sokolov AV. Hypochlorous acid as a precursor of free radicals in living systems. Biochemistry (Mosc). 2013;78(13):1466–1489. DOI: 10.1134/S0006297913130075

[2] Panasenko O.M., Gorudko I.V., Sokolov A.V. Hypochlorous acid as a precursor of free radicals in living systems // Biochemistry (Mosc). 2013. Vol. 78, No. 13. P. 1466–1489. DOI: 10.1134/S0006297913130075

[3] Stocker R, Keaney JF Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–1478. DOI: 10.1152/physrev.00047.2003

[4] Stocker R., Keaney J.F. Jr. Role of oxidative modifications in atherosclerosis // Physiol. Rev. 2004. Vol. 84, No. 4. P. 1381–1478. DOI: 10.1152/physrev.00047.2003

[5] Sokolov AV, Kostevich VA, Runova OL, et al. Proatherogenic modification of LDL by surface-bound myeloperoxidase. Chem Phys Lipids. 2014;180:72–80. DOI: 10.1016/j.chemphyslip.2014.02.006

[6] Sokolov A.V., Kostevich V.A., Runova O.L. et al. Proatherogenic modification of LDL by surface-bound myeloperoxidase // Chem. Phys. Lipids. 2014. Vol. 180. P. 72–80. DOI: 10.1016/j.chemphyslip.2014.02.006

[7] Ismael FO, Proudfoot JM, Brown BE, et al. Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis. Arch Biochem Biophys. 2015;573:40–51. DOI: 10.1016/j.abb.2015.03.008

[8] Ismael F.O., Proudfoot J.M., Brown B.E. et al. Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis // Arch. Biochem. Biophys. 2015. Vol. 573. P. 40–51. DOI: 10.1016/j.abb.2015.03.008

[9] Panasenko OM, Torkhovskaya TI, Sokolov AV, Gorudko IV. The role of halogenative stress in atherogenic modification of low-density lipoproteins. Biochemistry (Mosc). 2020;85(Suppl 1):S34–S55. DOI: 10.1134/S0006297920140035

[10] Panasenko O.M., Torkhovskaya T.I., Sokolov A.V., Gorudko I.V. The role of halogenative stress in atherogenic modification of low-density lipoproteins // Biochemistry (Mosc). 2020. Vol. 85, No. Suppl 1. P. S34–S55. DOI: 10.1134/S0006297920140035

[11] Teng N, Maghzal GJ, Talib J, et al. The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture. Redox Rep. 2017;22(2):51–73. DOI: 10.1080/13510002.2016.1256119

[12] Teng N., Maghzal G.J., Talib J. et al. The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture // Redox Rep. 2017. Vol. 22, No. 2. P. 51–73. DOI: 10.1080/13510002.2016.1256119

[13] Abdo AI, Rayner BS, van Reyk DM, Hawkins CL. Low-density lipoprotein modified by myeloperoxidase oxidants induces endothelial dysfunction. Redox Biol. 2017;13:623–632. DOI: 10.1016/j.redox.2017.08.004

[14] Abdo A.I., Rayner B.S., van Reyk D.M., Hawkins C.L. Low-density lipoprotein modified by myeloperoxidase oxidants induces endothelial dysfunction // Redox Biol. 2017. Vol. 13. P. 623–632. DOI: 10.1016/j.redox.2017.08.004

[15] Zhou L, Li C, Gao L, Wang A. High-density lipoprotein synthesis and metabolism (Review). Mol Med Rep. 2015;12(3):4015–4021. DOI: 10.3892/mmr.2015.3930

[16] Zhou L., Li C., Gao L., Wang A. High-density lipoprotein synthesis and metabolism (Review) // Mol. Med. Rep. 2015. Vol. 12, No. 3. P. 4015–4021. DOI: 10.3892/mmr.2015.3930

[17] Malle E, Marsche G, Panzenboeck U, Sattler W. Myeloperoxidase-mediated oxidation of high-density lipoproteins: Fingerprints of newly recognized potential proatherogenic lipoproteins. Arch Biochem Biophys. 2006;445(2):245–255. DOI: 10.1016/j.abb.2005.08.008

[18] Malle E., Marsche G., Panzenboeck U., Sattler W. Myeloperoxidase-mediated oxidation of high-density lipoproteins: Fingerprints of newly recognized potential proatherogenic lipoproteins // Arch. Biochem. Biophys. 2006. Vol. 445, No. 2. P. 245–255. DOI: 10.1016/j.abb.2005.08.008

[19] Schindhelm RK, van der Zwan LP, Teerlink T, Scheffer PG. Myeloperoxidase: A useful biomarker for cardiovascular disease risk stratification? Clin Chem. 2009;55(8):1462–1470. DOI: 10.1373/clinchem.2009.126029

[20] Schindhelm R.K., van der Zwan L.P., Teerlink T., Scheffer P.G. Myeloperoxidase: A useful biomarker for cardiovascular disease risk stratification? // Clin. Chem. 2009. Vol. 55, No. 8. P. 1462–1470. DOI: 10.1373/clinchem.2009.126029

[21] Urundhati A, Huang Y, Lupica JA, et al. Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particle. J Biol Chem. 2009;284(45):30825–30835. DOI: 10.1074/jbc.M109.047605

[22] Urundhati A., Huang Y., Lupica J.A. et al. Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particle // J. Biol. Chem. 2009. Vol. 284, No. 45. P. 30825–30835. DOI: 10.1074/jbc.M109.047605

[23] Hu J, Xi D, Zhao J, et al. High-density lipoprotein and inflammation and its significance to atherosclerosis. Am J Med Sci. 2016;352(4):408–415. DOI: 10.1016/j.amjms.2016.06.014

[24] Hu J., Xi D., Zhao J. et al. High-density lipoprotein and inflammation and its significance to atherosclerosis // Am. J. Med. Sci. 2016. Vol. 352, No. 4. P. 408–415. DOI: 10.1016/j.amjms.2016.06.014

[25] Singh V, Sharma R, Kumar A, Deedwania P. Low high-density lipoprotein cholesterol: Current status and future strategies for management. Vasc Health Risk Manag. 2010;6(1):979–996. DOI: 10.2147/VHRM.S5685

[26] Singh V., Sharma R., Kumar A., Deedwania P. Low high-density lipoprotein cholesterol: Current status and future strategies for management // Vasc. Health Risk Manag. 2010. Vol. 6, No. 1. P. 979–996. DOI: 10.2147/VHRM.S5685

[27] Acharjee S, Boden WE, Hartigan PM, et al. Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: A post-hoc analysis from the COURAGE trial (clinical outcomes utilizing revascularization and aggressive drug evaluation). J Am Coll Cardiol. 2013;62(20):1826–1833. DOI: 10.1016/j.jacc.2013.07.051

[28] Acharjee S., Boden W.E., Hartigan P.M. et al. Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: A post-hoc analysis from the COURAGE trial (clinical outcomes utilizing revascularization and aggressive drug evaluation) // J. Am. Coll. Cardiol. 2013. Vol. 62, No. 20. P. 1826–1833. DOI: 10.1016/j.jacc.2013.07.051

[29] Turner S, Voogt J, Davidson M, et al. Measurement of reverse cholesterol transport pathways in humans: in vivo rates of free cholesterol efflux, esterification, and excretion. J Am Heart Assoc. 2012;1(4):e001826. DOI: 10.1161/jaha.112.001826

[30] Turner S., Voogt J., Davidson M. et al. Measurement of reverse cholesterol transport pathways in humans: in vivo rates of free cholesterol efflux, esterification, and excretion // J. Am. Heart Assoc. 2012. Vol. 1, No. 4. P. e001826. DOI: 10.1161/jaha.112.001826

[31] Connelly MA, Shalaurova I, Otvos JD. High-density lipoprotein and inflammation in cardiovascular disease. Transl Res. 2016;173:7–18. DOI: 10.1016/J.TRSL.2016.01.006

[32] Connelly M.A., Shalaurova I., Otvos J.D. High-density lipoprotein and inflammation in cardiovascular disease // Transl. Res. 2016. Vol. 173. P. 7–18. DOI: 10.1016/J.TRSL.2016.01.006

[33] Khine HW, Teiber JF, Haley RW, et al. Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study. Atherosclerosis. 2017;263:156–162. DOI: 10.1016/j.atherosclerosis.2017.06.007

[34] Khine H.W., Teiber J.F., Haley R.W. et al. Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study // Atherosclerosis. 2017. Vol. 263. P. 156–162. DOI: 10.1016/j.atherosclerosis.2017.06.007

[35] Kimak E, Zięba B, Duma D, Solski J. Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease. Lipids Health Dis. 2018;17(1):71. DOI: 10.1186/s12944-018-0718-4

[36] Kimak E., Zięba B., Duma D., Solski J. Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease // Lipids Health Dis. 2018. Vol. 17, No. 1. P. 71. DOI: 10.1186/s12944-018-0718-4

[37] Escobar E. Hypertension and coronary heart disease. J Hum Hypertens. 2002;16 Suppl 1:S61–63. DOI: 10.1038/sj.jhh.1001345

[38] Escobar E. Hypertension and coronary heart disease // J. Hum. Hypertens. 2002. Vol. 16 Suppl 1. P. S61–63. DOI: 10.1038/sj.jhh.1001345

[39] Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407–477. DOI: 10.1093/eurheartj/ehz425

[40] Knuuti J., Wijns W., Saraste A. et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes // Eur. Heart J. 2020. Vol. 41, No. 3. P. 407–477. DOI: 10.1093/eurheartj/ehz425

[41] Franck T, Minguet G, Delporte C, et al. An immunological method to combine the measurement of active and total myeloperoxidase on the same biological fluid, and its application in finding inhibitors which interact directly with the enzyme. Free Radic Res. 2015;49(6):790–799. DOI: 10.3109/10715762.2015.1027197

[42] Franck T., Minguet G., Delporte C. et al. An immunological method to combine the measurement of active and total myeloperoxidase on the same biological fluid, and its application in finding inhibitors which interact directly with the enzyme // Free Radic. Res. 2015. Vol. 49, No. 6. P. 790–799. DOI: 10.3109/10715762.2015.1027197

[43] Sokolov AV, Kostevich VA, Gorbunov NP, et al. A link between active myeloperoxidase and chlorinated ceruloplasmin in blood plasma of patients with cardiovascular diseases. Medical Immunology (Russia). 2018;20(5):699–710. (In Russ.). DOI: 10.15789/1563-0625-2018-5-699-710

[44] Соколов А.В., Костевич В.А., Горбунов Н.П. и др. Связь между активной миелопероксидазой и хлорированным церулоплазмином в плазме крови пациентов с сердечно-сосудистыми заболеваниями // Медицинская иммунология. 2018. Т. 20, № 5. С. 699–710. DOI: 10.15789/1563-0625-2018-5-699-710

[45] Sokolov AV, Kostevich VA, Kozlov SO, et al. Kinetic method for assaying the halogenating activity of myeloperoxidase based on reaction of celestine blue B with taurine halogenamines. Free Radic Res. 2015;49(6):777–789. DOI: 10.3109/10715762.2015.1017478

[46] Sokolov A.V., Kostevich V.A., Kozlov S.O. et al. Kinetic method for assaying the halogenating activity of myeloperoxidase based on reaction of celestine blue B with taurine halogenamines // Free Radic. Res. 2015. Vol. 49, No. 6. P. 777–789. DOI: 10.3109/10715762.2015.1017478

[47] Panasenko OM, Mikhalchik EV, Gorudko IV, et al. The effects of antioxidants and hypohalous acid scavengers on neutrophil activation by hypochlorous acid-modified low-density lipoproteins. Biophysics. 2016;61(3):420–428. DOI: 10.1134/S0006350916030131

[48] Панасенко О.М., Михальчик Е.В., Горудко И.В. и др. Влияние антиоксидантов и скавенджеров гипогалоидных кислот на активацию нейтрофилов липопротеинами низкой плотности, модифицированными гипохлоритом // Биофизика. 2016. Т. 61, № 3. С. 500–509.

[49] Sokolov AV, Gorbunov NP, Kostevich VA, Panasenko OM. Characteristics and prospects of using monoclonal antibodies against myeloperoxidase. Bioradicals and Antioxidants. 2018;5(3):65–67. (In Russ.)

[50] Соколов А.В., Горбунов Н.П., Костевич В.А., Панасенко О.М. Характеристика и перспективы применения моноклональных антител против миелопероксидазы // Биорадикалы и антиоксиданты. 2018. Т. 5, № 3. С. 65–67.

[51] Sokolov AV, Kostevich VA, Zakharova ET, et al. Interaction of ceruloplasmin with eosinophil peroxidase as compared to its interplay with myeloperoxidase: reciprocal effect on enzymatic properties. Free Radic Res. 2015;49(6):800–811. DOI: 10.3109/10715762.2015.1005615

[52] Sokolov A.V., Kostevich V.A., Zakharova E.T. et al. Interaction of ceruloplasmin with eosinophil peroxidase as compared to its interplay with myeloperoxidase: reciprocal effect on enzymatic properties // Free Radic. Res. 2015. Vol. 49, No. 6. P. 800–811. DOI: 10.3109/10715762.2015.1005615

[53] Huang Y, Wu Z, Riwanto M, et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. J Clin Invest. 2013;123(9):3815–3828. DOI: 10.1172/JCI67478

[54] Huang Y., Wu Z., Riwanto M. et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex // J. Clin. Invest. 2013. Vol. 123, No. 9. P. 3815–3828. DOI: 10.1172/JCI67478

[55] Gach O, Brogneaux C, Franck T, et al. Active and total myeloperoxidase in coronary artery disease and relation to clinical instability. Acta Cardiol. 2015;70(5):522–527. DOI: 10.2143/AC.70.5.3110512

[56] Gach O., Brogneaux C., Franck T. et al. Active and total myeloperoxidase in coronary artery disease and relation to clinical instability // Acta Cardiol. 2015. Vol. 70, No. 5. P. 522–527. DOI: 10.2143/AC.70.5.3110512

[57] Trentini A, Rosta V, Spadaro S, et al. Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: Role of MPO specific activity in coronary artery disease. Clin Chem Lab Med. 2020;58(10):1749–1758. DOI: 10.1515/cclm-2019-0817

[58] Trentini A., Rosta V., Spadaro S. et al. Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: Role of MPO specific activity in coronary artery disease // Clin. Chem. Lab. Med. 2020. Vol. 58, No. 10. P. 1749–1758. DOI: 10.1515/cclm-2019-0817

[59] Afshinnia F, Zeng L, Byun J, et al. Myeloperoxidase levels and its product 3-chlorotyrosine predict chronic kidney disease severity and associated coronary artery disease. Am J Nephrol. 2017;46(1):73–81. DOI: 10.1159/000477766

[60] Afshinnia F., Zeng L., Byun J. et al. Myeloperoxidase levels and its product 3-chlorotyrosine predict chronic kidney disease severity and associated coronary artery disease // Am. J. Nephrol. 2017. Vol. 46, No. 1. P. 73–81. DOI: 10.1159/000477766

[61] Exner M, Minar E, Mlekusch W, et al. Myeloperoxidase predicts progression of carotid stenosis in states of low high-density lipoprotein cholesterol. J Am Coll Cardiol. 2006;47(11):2212–2218. DOI: 10.1016/j.jacc.2006.01.067

[62] Exner M., Minar E., Mlekusch W. et al. Myeloperoxidase predicts progression of carotid stenosis in states of low high-density lipoprotein cholesterol // J. Am. Coll. Cardiol. 2006. Vol. 47, No. 11. P. 2212–2218. DOI: 10.1016/j.jacc.2006.01.067

[63] Manchanda K, Kolarova H, Kerkenpaß C, et al. MPO (Myeloperoxidase) reduces endothelial glycocalyx thickness dependent on its cationic charge. Arterioscler Thromb Vasc Biol. 2018;38(8):1859–1867. DOI: 10.1161/ATVBAHA.118.311143

[64] Manchanda K., Kolarova H., Kerkenpaß C. et al. MPO (Myeloperoxidase) reduces endothelial glycocalyx thickness dependent on its cationic charge // Arterioscler. Thromb. Vasc. Biol. 2018. Vol. 38, No. 8. P. 1859–1867. DOI: 10.1161/ATVBAHA.118.311143

[65] Grigorieva DV, Gorudko IV, Kostevich VA, et al. Myeloperoxidase activity in blood plasma as a criterion of therapy for patients with cardiovascular disease. Biomeditsinskaya khimiya. 2016;62(3):318–324. (In Russ.). DOI: 10.18097/PBMC20166203318

[66] Григорьева Д.В., Горудко И.В., Костевич В.А. и др. Активность миелопероксидазы в плазме крови как критерий эффективности лечения пациентов с сердечно-сосудистыми заболеваниями // Биомедицинская химия. 2016. Т. 62, № 3. С. 318–324. DOI: 10.18097/PBMC20166203318

RIGHTS & PERMISSIONS

Churashova I.A., Sokolov A.V., Kostevich V.A., Gorbunov N.P., Runova O.L., Firova E.M., Vasilyev V.B.