Immunological Reactivity and Intensity of Oxidative Stress in Stable Coronary Artery Disease

  • Tetiana І. Gavrilenko SI “National Scientific Center “The M.D. Strazhesko Institute of Cardiology, Clinical and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • Oleksandr M. Lomakovskyi SI “National Scientific Center “The M.D. Strazhesko Institute of Cardiology, Clinical and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • Olena A. Pidgaina SI “National Scientific Center “The M.D. Strazhesko Institute of Cardiology, Clinical and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • Olga V. Rasputniak National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
  • Nataliia O. Ryzhkova SI “National Scientific Center “The M.D. Strazhesko Institute of Cardiology, Clinical and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • Natalia V. Grechkovskaya Bogomolets National Medical University, Kyiv, Ukraine
Keywords: coronary atherosclerosis, immunopathological reactions, immune inflammation, CD40/CD40L system, antiperoxide protection


The aim. To analyze the relationship between immune response factors and the intensity of oxidation of lipoproteins and proteins in patients with stable coronary artery disease (CAD) to clarify the pathogenesis of coronary atherosclerosis.

Materials and methods. A total of 179 patients with stable CAD of II-IV functional class, mean age 56 (49-62) years (main group) and 30 healthy individuals, mean age 49 (45-53) years (control group) were examined. The material for immunological research was peripheral venous blood. To determine the indicators of immunity, flow laser cytometry and enzyme-linked immunosorbent assay were used. Spectrophotometric and fluorometric methods were used to determine the levels of intermediate and final oxidation products of lipids and proteins, as well as antioxidant protection enzymes in the blood serum and in atherogenic lipoproteins.

Results. A direct relationship between the activity of lipoprotein peroxidation and protein oxidation with a cell-type immune response and immune inflammation was revealed.

Conclusions. The high intensity of lipid peroxidation and protein oxidation in patients with stable CAD (stable angina pectoris) is combined with significant activation of the T-cell component of the immune response (in terms of the ratio of helper and cytotoxic subpopulations of T-lymphocytes, high concentrations of pro-inflammatory cytokines, the state of the CD40/CD40L system, the level of expression of the CD95 apoptosis marker on cells), which indicates interdependence of T-cell immunity and oxidative stress in the pathogenesis of atherosclerosis. The dependence of the hyperproduction of pro-inflammatory cytokines by mononuclear blood cells on free radical oxidation of proteins, peroxidation of apoB proteins and the intensity of antiperoxide protection (catalase and superoxide dismutase enzymes) in patients with stable CAD indicates a contribution to the presence of oxidative stress and the development of immune inflammation. A comprehensive study of the factors of immunological reactivity, the violation of which can lead to the development of immunopathological reactions, and the intensity of oxidation of lipoproteins and proteins in patients with stable CAD helps to clarify the pathogenetic relationship between chronic immune inflammation, endothelial dysfunction and oxidative stress, and also substantiates the expediency of general therapeutic approaches to the treatment of CAD.


  1. Libby P. The changing landscape of atherosclerosis. Nature. 2021;592(7855):524-533.
  2. Mallat Z, Binder CJ. The why and how of adaptive immune responses in ischemic cardiovascular disease. Nat Cardiovasc Res. 2022;1:431-444.
  3. Bjorkegren JLM, Kovacic JC, Dudley JT, Schadt EE. Genome-Wide Significant Loci: How Important Are They? Systems Genetics to Understand Heritability of Coronary Artery Disease and Other Common Complex Disorders. J Am Coll Cardiol. 2015;65(8):830-845.
  4. Porsch F, Mallat Z, Binder CJ. Humoral immunity in atherosclerosis and myocardial infarction: from B cells to antibodies. Cardiovasc Res. 2021;117(13):2544-2562.
  5. Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020;41(24):2313-2330.
  6. Maaninka K, Nguyen SD, Mäyränpää MI, Plihtari R, Rajamäki K, Lindsberg PJ, et al. Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding. Atherosclerosis. 2018;275:390-399.
  7. Öörni K, Kovanen PT. Aggregation Susceptibility of Low- Density Lipoproteins-A Novel Modifiable Biomarker of Cardiovascular Risk. J Clin Med. 2021 Apr 19;10(8):1769.
  8. Heffron SP, Ruuth MK, Xia Y, Hernandez G, Äikäs L, Rodriguez C, et al. Low-density lipoprotein aggregation predicts adverse cardiovascular events in peripheral artery disease. Atherosclerosis. 2021;316:53-57.
  9. Ruuth M, Nguyen SD, Vihervaara T, Hilvo M, Laajala TD, Kondadi PK, et al. Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths. Eur Heart J. 2018;39(27):2562-2573.
  10. Virella G, Wilson K, Elkes J, Hammad SM, Rajab HA, Li Y, et al. Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human macrophages. Clin Immunol. 2018;187:1-9.
  11. Gonen A, Choi SH, Miu P, Agatisa-Boyle C, Acks D, Taylor AM, et al. A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma. J Lipid Res. 2019;60(2):436-445.
  12. Orekhov AN, Sobenin IA. Modified lipoproteins as biomarkers of atherosclerosis. Front Biosci (Landmark Ed). 2018;23(8):1422-1444.
  13. Tailleux A, Torpier G, Caron B, Fruchart JC, Fievet C. Immunological properties of apoB-containing lipoprotein particles in human atherosclerotic arteries. J Lipid Res. 1993;34(5):719-728.
  14. Rhoads JP, Lukens JR, Wilhelm AJ, Moore JL, Mendez-Fernandez Y, Kanneganti TD, et al. Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9. J Immunol. 2017;198(5):2105-2114.
  15. Orekhov AN, Oishi Y, Nikiforov NG, Zhelankin AV, Dubrovsky L, Sobenin IA, et al. Modified LDL Particles Activate Inflammatory Pathways in Monocyte-derived Macrophages: Transcriptome Analysis. Curr Pharm Des. 2018;24(26):3143-3151.
  16. Tuñón J, Badimón L, Bochaton-Piallat ML, Cariou B, Daemen MJ, Egido J, et al. Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology. Cardiovasc Res. 2019;115(1):10-19.
  17. Roy P, Orecchioni M, Ley K. How the immune system shapes atherosclerosis: roles of innate and adaptive immunity. Nat Rev Immunol. 2022;22(4):251-265.
  18. Rieckmann M, Delgobo M, Gaal C, Büchner L, Steinau P, Reshef D, et al. Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses. J Clin Invest. 2019;129(11):4922-4936.
  19. Kyaw T, Loveland P, Kanellakis P, Cao A, Kallies A, Huang AL, et al. Alarmin-activated B cells accelerate murine atherosclerosis after myocardial infarction via plasma cell-immunoglobulin-dependent mechanisms. Eur Heart J. 2021;42(9):938-947.
  20. Sage AP, Tsiantoulas D, Binder CJ, Mallat Z. The role of B cells in atherosclerosis. Nat Rev Cardiol. 2019;16(3):180-196.
  21. Zernecke A, Winkels H, Cochain C, Williams JW, Wolf D, Soehnlein O, et al. Meta-Analysis of Leukocyte Diversity in Atherosclerotic Mouse Aortas. Circ Res. 2020;127(3):402-426.
  22. Ketelhuth DF, Hansson GK. Adaptive Response of T and B Cells in Atherosclerosis. Circ Res. 2016;118(4):668-678.
  23. Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 2020;17(7):387-401.
  24. Kimura T, Kobiyama K, Winkels H, Tse K, Miller J, Vassallo M, et al. Regulatory CD4+ T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B. Circulation. 2018;138(11):1130-1143.
  25. Yang TC, Chang PY, Lu SC. L5-LDL from ST-elevation myocardial infarction patients induces IL-1β production via LOX-1 and NLRP3 inflammasome activation in macrophages. Am J Physiol Heart Circ Physiol. 2017;312(2):H265-H274.
  26. Chang CK, Chen PK, Lan JL, Chang SH, Hsieh TY, Liao PJ, et al. Association of Electronegative LDL with Macrophage Foam Cell Formation and CD11c Expression in Rheumatoid Arthritis Patients. Int J Mol Sci. 2020 Aug 16;21(16):5883.
  27. Luchetti F, Crinelli R, Nasoni MG, Benedetti S, Palma F, Fraternale A, et al. LDL receptors, caveolae and cholesterol in endothelial dysfunction: oxLDLs accomplices or victims? Br J Pharmacol. 2021;178(16):3104-3114.
  28. Wolf D, Ley K. Immunity and Inflammation in Atherosclerosis. Circ Res. 2019;124(2):315-327.
  29. Prasad A, Clopton P, Ayers C, Khera A, De Lemos JA, Witztum JL, et al. Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events. Arterioscler Thromb Vasc Biol. 2017;37(6):1213-1221.
  30. Asciutto G, Dias NV, Edsfeldt A, Alm R, Fredrikson GN, Gonçalves I, et al. Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy. Atherosclerosis. 2015;239(2):289-294.
  31. Kuznetsova LV, Babadzhan VD, Frolov VM, Kravchun PH, Kuznetsov HV, Kurchenko AI, et al. [Clinical and laboratory immunology]. Kuznetsova LV, editor. Kyiv; 2012. Ukrainian.
  32. Hawley TS, Hawley RG, editors. Flow Cytometry Protocols. 4th ed. New York: Humana New York; 2017.
  33. Lunova HH, editor. [Clinical biochemistry]. 1st volume. Lviv;2021. Ukrainian.
  34. Lomakovsky OM. [Relationship of dyslipidemia and oxidative stress with the state of humoral immune in patients with IHD with stable angina]. Ukrainskyi revmatolohichnyi zhurnal. 2022;(88(2)):1-6. Ukrainian.
  35. Bosmans LA, Bosch L, Kusters PJH, Lutgens E, Seijkens TTP. The CD40-CD40L Dyad as Immunotherapeutic Target in Cardiovascular Disease. J Cardiovasc Transl Res. 2021;14(1):13-22.
How to Cite
GavrilenkoT. І., Lomakovskyi, O. M., Pidgaina, O. A., Rasputniak, O. V., Ryzhkova, N. O., & Grechkovskaya, N. V. (2023). Immunological Reactivity and Intensity of Oxidative Stress in Stable Coronary Artery Disease. Ukrainian Journal of Cardiovascular Surgery, 31(3), 22-30.