Features of the relationship between clinical and laboratory, ultrasound signs of atherosclerosis and antioxidant defense in patients with comorbid pathology


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Resumo

The ambiguity of data on Nrf2-mediated redox-sensitive signaling pathways participation in atherogenesis and the progression of atherosclerosis determines the need to search for new data on the mechanisms of cause-effect relationships of these processes. The aim of the research was to study the features of clinical and laboratory markers of atherosclerosis and the level of genes expression of the antioxidant defense system (NRF2, HMOX1, NQO1, GSTP1) in correlation to the echoscopically verified degree of carotid artery (CA) stenosis. Material and methods. The study included 160 patients from the clinic of the Federal research center for fundamental and translational Medicine aged from 35 to 78 years. They underwent clinical and laboratory diagnostics, ultrasound examination of brachiocephalic arteries, assessment of the expression of genes involved in the formation of antioxidant protection (NRF2, NQO1, HMOX1, GSTP1) using RT-PCR methodic. Results. It was found that in peripheral blood leukocytes of patients with verified CA atherosclerosis, the expression of GSTP1, NQO1, and NRF2 genes is reduced (by 49, 51, and 44%, respectively), while the mRNA contained amount of the HMOX1 gene is not changed. A correlation was revealed between the severity of expression of genes GSTP1, HMOX1, NQO1, NRF2, indicators 77 of blood lipid spectrum, as well as the degree of CA stenosis: an inverse correlation between the expression of NQO1 gene and the percentage of stenosis in the left common CA, expression of GSTP1 gene and the atherogenic coefficient, a direct relationship between the level of mRNA of the NRF2 gene and the concentration of high density lipoproteins (HDL). A direct correlation was found between the concentration of triglycerides and the thickness of the «intima-media» complex, the content of total cholesterol and the blood flow rate in the right internal CA, an inverse correlation between the level of HDL, as well as the concentration of apolipoprotein A and the thickness of the «intima-media» complex of the common CA. Conclusion. Complex pathogenetic interrelationships of the expression of antioxidant defense genes, the degree of atherosclerotic stenosis and blood flow velocity of CA, as well as indexes of blood lipid spectrum are shown.

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Sobre autores

V. Polyakov

Federal Research Center for Fundamental and Translational Medicine

Email: vpolyakov15@mail.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

I. Kovrigin

Federal Research Center for Fundamental and Translational Medicine

Email: ahiues9@bk.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

P. Kozhin

Federal Research Center for Fundamental and Translational Medicine

Email: kozhinpm@centercem.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

Yu. Nikolaev

Federal Research Center for Fundamental and Translational Medicine

Email: nicol@centercem.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

A. Malov

Federal Research Center for Fundamental and Translational Medicine

Email: malov_as@cnmt.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

E. Sevostyanova

Federal Research Center for Fundamental and Translational Medicine

Email: luck.nsk@rambler.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

E. Menschikova

Federal Research Center for Fundamental and Translational Medicine

Email: lemen@centercem.ru
630117, Novosibirsk, 2 Timakova Str. Tel.: +7 (963) 942-35-25

Bibliografia

  1. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006; 47(8 Suppl): 07-12. doi: 10.1016/j.jacc.2005.09.068.
  2. Rafieian-Kopaei M., Setorki M., Doudi M. et al. Atherosclerosis: Process, indicators, risk factors and new hopes. Int J Prev Med. 2014; 5(8): 927-46.
  3. Зенков Н.К., Колпаков А.Р., Меньщикова Е.Б. Редокс-чувствительная система Keap1/Nrf2/ARE как фармакологическая мишень при сердечно-сосудистой патологии. Сибирский научный медицинский журнал. 2015; 5: 5-25. @@Zenkov N.K., Kolpakov A.R., Menshchikova E.B. The redox-sensitive Keap1/Nrf2/ARE system as a pharmacological target in cardiovascular pathology. Sibirskiy nauchnyy medicinsky zhurnal = Siberian Scientific Medical Journal. 2015; 5: 5-25 (In Russ.).
  4. Tian C., Gao L., Zucker I.H. Regulation of Nrf2 signaling pathway in heart failure: Role of extracellular vesicles and non-coding RNAs. Free Radic Biol Med. 2021; 167: 218-31. doi: 10.1016/j.freeradbiomed.2021.03.013.
  5. Souilhol C., Harmsen M.C., Evans P.C., Krenning G. Endothelial-mesenchymal transition in atherosclerosis. Cardiovasc Res. 2018; 114(4): 565-77. doi: 10.1093/cvr/cvx253.
  6. Kloska D., Kopacz A., Piechota-Polanczyk A. et al. Nrf2 in aging - focus on the cardiovascular system. Vascul Pharmacol. 2019; 112: 42-53. doi: 10.1016/j.vph.2018.08.009.
  7. Wei Y., Gong J., Thimmulappa R. K. et al. Nrf2 acts cell-autonomously in endothelium to regulate tip cell formation and vascular branching. Proc Natl Acad Sci USA. 2013; 110(41): E3910-18. doi: 10.1073/pnas.1309276110.
  8. Ahmed S.M.U., Luo L., Namani A. et al. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(2): 585-97. doi: 10.1016/j.bbadis.2016.11.005.
  9. Holloway P.M., Gillespie S., Becker F. et al. Sulforaphane induces neurovascular protection against a systemic inflammatory challenge via both Nrf2-dependent and independent pathways. Vascul Pharmacol. 2016; 85: 29-38. doi: 10.1016/j.vph.2016.07.004.
  10. Takabe W., Warabi E., Noguchi N. Anti-atherogenic effect of laminar shear stress via Nrf2 activation. Antioxid Redox Signal. 2011; 15(5): 1415-26. doi: 10.1089/ars.2010.3433.
  11. Zhang Z., Zhou S., Jiang X. et al. The role of the Nrf2/Keap1 pathway in obesity and metabolic syndrome. Rev Endocr Metab Disord. 2015; 16(1): 35-45. doi: 10.1007/s11154-014-9305-9.
  12. Sachdeva A., Cannon C.P., Deedwania P.C. et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136.905 hospitalizations in get with the guidelines. Am Heart J. 2009; 157(1): 111-17.e2. doi: 10.1016/j.ahj.2008.08.010.
  13. Carmena R., Duriez P., Fruchart J.C. Atherogenic lipoprotein particles in atherosclerosis. Circulation. 2004; 109(23 Suppl 1): III2-7. doi: 10.1161/01.CIR.0000131511.50734.44.
  14. Berneis K.K., Krauss R.M. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res. 2002; 43(9): 1363-79. doi: 10.1194/jlr.r200004-jlr200.
  15. Kwiterovich P.O. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. Am J Cardiol. 2002; 90(8A): 30i-47i. doi: 10.1016/s0002-9149(02)02749-2.
  16. Krauss R.M. Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol. 2010; 21(4): 305-11. doi: 10.1097/ MOL.0b013e32833b7756.
  17. Abdolmaleki F., Hayat S.M.G., Bianconi V. et al. Atherosclerosis and immunity: A perspective. Trends Cardiovasc Med. 2019; 29(6): 363-71. doi: 10.1016/j.tcm.2018.09.017.
  18. Lacolley P., Regnault V., Nicoletti A. et al. The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res. 2012; 95(2):194-204. doi: 10.1093/cvr/cvs135.
  19. Badran A., Nasser A. S., Mesmar J. et al. Reactive oxygen species: Modulators of phenotypic switch of vascular smooth muscle cells. Int J Mol Sci. 2020; 21(22): 8764. doi: 10.3390/ijms21228764.
  20. Ashino T., Yamamoto M., Yoshida T., Numazawa S. Redox-sensitive transcription factor Nrf2 regulates vascular smooth muscle cell migration and neointimal hyperplasia. Arterioscler Thromb Vasc Biol. 2013; 33(4): 760-68. doi: 10.1161/ATVBAHA.112.300614.
  21. Cheng C., Haasdijk R. A., Tempel D. et al. PDGF-induced migration of vascular smooth muscle cells is inhibited by heme oxygenase-1 via VEGFR2 upregulation and subsequent assembly of inactive VEGFR2/PDGFRB heterodimers. Arterioscler Thromb Vasc Biol. 2012; 32(5): 1289-98. doi: 10.1161/ATVBAHA.112.245530.
  22. Генкель Б.Б., Салашенко А.О., Алексеева О.А., Шапошник И.И. Комплексная оценка сосудистой жесткости у больных атеросклерозом периферических артерий. Атеросклероз и дислипидемии. 2016; 4: 49-56. [Genkel B.B., Malashenko A.O., Alekseeva O.A., Shaposhnik I.I. Complex assessment of vascular stiffness in patients with atherosclerosis of peripheral arteries. Ateroskleroz i dislipidemii = Atherosclerosis and dyslipidemia. 2016; 4: 49-56 (In Russ.)].
  23. Ding Y., Zhang B., Zhou K. et al. Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: role of Nrf2 activation. Int J Cardiol. 2014; 175(3): 508-14. doi: 10.1016/j.ijcard.2014.06.045.
  24. Hur K.Y., Kim S.H., Choi M.A. et al. Protective effects of magnesium lithospermate B against diabetic atherosclerosis via Nrf2-ARE-NQO1 transcriptional pathway. Atherosclerosis. 2010; 211(1): 69-76. doi: 10.1016/j.atherosclerosis.2010.01.035.
  25. Zenkov N.K., Kozhin P.M., Chechushkov A.V. et al. Mazes of Nrf2 regulation. Biochemistry (Moscow). 2017; 82(5): 556-64. doi: 10.1134/ s0006297917050030.
  26. Liu T., Lv Y.F., Zhao J.L. et al. Regulation of Nrf2 by phosphorylation: Consequences for biological function and therapeutic implications. Free Radic Biol Med. 2021; 168: 129-41. doi: 10.1016/j.freeradbiomed.2021.03.034.
  27. Libby P., Ridker P.M., Hansson G.K. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011; 473(7347): 317-25. doi: 10.1038/nature10146.
  28. Itabe H., Sawada N., Makiyama T., Obama T. Structure and dynamics of oxidized lipoproteins in vivo: Roles of high-density lipoprotein. Biomedicines. 2021; 9(6): 655. doi: 10.3390/biomedicines9060655.

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