Воспалительные заболевания кишечника (ВЗК) могут являться причиной раннего атеросклероза. Существует корреляция между активностью воспалительного процесса при ВЗК и сердечно-сосудистыми событиями. Хроническое воспаление может приводить к эндотелиальной дисфункции. В обзоре обсуждаются механизмы, лежащие в основе связи ВЗК и атеросклероза, роль врожденного и гуморального иммунитета, кишечной микробиоты и биомаркеров (С-реактивного белка, гомоцистеина и др.), а также рассматриваются возможности ранней инструментальной диагностики сосудистого повреждения у пациентов с ВЗК с помощью измерения толщины комплекса интима–медиа сонной артерии и определения скорости каротидно-феморальной пульсовой волны. Подчеркивается необходимость активной профилактики сердечно-сосудистых заболеваний у данной группы пациентов, в том числе посредством контроля активности воспаления, а также включения ВЗК в один из факторов риска сердечно-сосудистых заболеваний.
Ключевые слова: воспалительные заболевания кишечника, хроническое воспаление, атеросклероз, эндотелиальная дисфункция, кишечная микробиота, биомаркеры, толщина комплекса интима–медиа, артериальная жесткость, скорость распространения пульсовой волны.
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Inflammatory bowel disease (IBD) can cause early atherosclerosis. There is a correlation between inflammatory activity in IBD and cardiovascular events. Chronic inflammation can lead to endothelial dysfunction. This review discusses the possibilities of the mechanisms underlying the relationship between IBD and atherosclerosis, the role of innate and humoral immunity, intestinal microbiota, biomarkers (C-reactive protein, homocysteine, etc.), as well as the possibility of early instrumental diagnosis of subclinical manifestations of atherosclerosis in patients with IBD by measuring carotid intima–media thickness and aortic pulse wave velocity. The need for active prevention of cardiovascular diseases in this group of patients is emphasized, including through the control of inflammation activity, as well as the inclusion of IBD in one of the risk factors for cardiovascular diseases.
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DOI:10.7759/cureus.10544
2. Garber A, Regueiro M. Extraintestinal Manifestations of Inflammatory Bowel Disease: Epidemiology, Etiopathogenesis, and Management. Curr Gastroenterol Rep. 2019;21(7). DOI:10.1007/s11894-019-0698-1
3. Harbord M, Annese V, Vavricka SR, et al. The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohns Colitis. 2016;10(3):239-54.
DOI:10.1093/ecco-jcc/jjv213
4. Aarestrup J, Jess T, Kobylecki CJ, et al. Cardiovascular Risk Profile Among Patients With Inflammatory Bowel Disease: A Population-based Study of More Than 100 000 Individuals. J Crohns Colitis. 2019;13(3):319-23. DOI:10.1093/ecco-jcc/jjy164.
5. Panhwar MS, Mansoor E, Al-Kindi SG, et al. Risk of Myocardial Infarction in Inflammatory Bowel Disease: A Population-based National Study. Inflamm Bowel Dis. 2019;25(6):1080-7.
DOI:10.1093/ibd/izy354
6. Czubkowski P, Osiecki M, Szymańska E, Kierkuś J. The risk of cardiovascular complications in inflammatory bowel disease. Clin Exp Med. 2020;20(4):481-91. DOI:10.1007/s10238-020-00639-y
7. Zanoli L, Mikhailidis DP, Bruno RM, et al. Aortic Stiffening Is an Extraintestinal Manifestation of Inflammatory Bowel Disease: Review of the Literature and Expert Panel Statement. Angiology. 2020;71(8):689-97. DOI:10.1177/0003319720918509
8. Bernstein CN, Blanchard JF, Houston DS. The incidence of deep venous thrombosis and pulmonary embolism among patients with infammatory bowel disease: a population-based cohort study. Thromb Haemost. 2001;85(3):430-4.
9. Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375(9715):657-63. DOI:10.1016/S0140-6736(09)61963-2
10. Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut. 2004;53(4):542-8. DOI:10.1136/gut.2003.025411
11. Pepe M, Carulli E, Forleo C, et al. Inflammatory Bowel Disease and Acute Coronary Syndromes: From Pathogenesis to the Fine Line between Bleeding and Ischemic Risk. Inflamm Bowel Dis. 2021;27(5):725-31. DOI:10.1093/ibd/izaa160
12. Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica. 2000;85(9):967-72. PMID: 10980636.
13. Stocker R, Keaney JF. New insights on oxidative stress in the artery wall. J Thromb Haemost. 2005;3(8):1825-34.
DOI:10.1111/j.1538-7836.2005.01370.x
14. Sokolova LK, Pushkarev VM, Pushkarev VV, et al. Diabetes mellitus and atherosclerosis. The role of inflammatory processes in pathogenesis (literature review). Int J Endocrinol. 2017;13(7):486-98. DOI:10.22141/2224-0721.13.7.2017.115747
15. Van Leuven SI, Hezemans R, Levels JH, et al. Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease.
J Lipid Res. 2007;48(12):2640-6. DOI:10.1194/jlr.M700176-JLR20
16. Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017;120(7):1183-96.
DOI:10.1161/CIRCRESAHA.117.309715
17. Van der Sloot KWJ, Amini M, Peters V, et al. Inflammatory Bowel Diseases: Review of Known Environmental Protective and Risk Factors Involved. Inflamm Bowel Dis. 2017;23(9):1499-509.
DOI:10.1097/MIB.0000000000001217
18. Underwood MA. Intestinal dysbiosis: novel mechanisms by which gut microbes trigger and prevent disease. Prev Med. 2014;65:133-7. DOI:10.1016/j.ypmed.2014.05.010
19. Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol.
2013;13(5):321-35. DOI:10.1038/nri3430
20. Lorenz RG, Chaplin DD, McDonald KG, et al. Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin beta receptor, and TNF receptor I function. J Immunol. 2003;170(11):5475-82.
DOI:10.4049/jimmunol.170.11.5475
21. Diehl GE, Longman RS, Zhang JX, et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature. 2013;494(7435):116-20. DOI:10.1038/nature11809
22. Wrzosek L, Miquel S, Noordine ML, et al. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 2013;11:61.
DOI:10.1186/1741-7007-11-61
23. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol. 2017;14(10):573-84. DOI:10.1038/nrgastro.2017.88
24. Biedermann L, Fournier N, Misselwitz B, et al. High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation – Data from the Swiss IBD Cohort Study [published correction appears in J Crohns Colitis. 2016 Jun;10(6):754]. J Crohns Colitis. 2015;9(10):819-29. DOI:10.1093/ecco-jcc/jjv113
25. Bastida G, Beltrán B. Ulcerative colitis in smokers, non-smokers and ex-smokers. World J Gastroenterol. 2011;17(22):2740-7.
DOI:10.3748/wjg.v17.i22.2740
26. Biondi RB, Salmazo PS, Bazan SGZ, et al. Cardiovascular risk in individuals with inflammatory bowel disease. Clin Exp Gastroenterol. 2020;13:107-13. DOI:10.2147/CEG.S243478
27. Cappello M, Licata A, Calvaruso V, et al. Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease. Eur J Intern Med. 2017;37:83-9. DOI:10.1016/j.ejim.2016.10.004
28. Kakodkar S, Mutlu EA. Diet as a Therapeutic Option for Adult Inflammatory Bowel Disease. Gastroenterol Clin North Am. 2017;46(4):745-67. DOI:10.1016/j.gtc.2017.08.016
29. Shon WJ, Jung MH, Choi EY, Shin DM. Sugar-sweetened Beverage and High Fat Diet Consumption Harmfully Alters Gut Microbiota and Promotes Gut Inflammation
(P20-041-19). Curr Dev Nutr. 2019;3(Suppl. 1):nzz040.P20-041-19.
DOI:10.1093/cdn/nzz040.P20-041-19
30. Bigeh A, Sanchez A, Maestas C, Gulati M. Inflammatory Bowel Disease & The Risk for Cardiovascular Disease: Does All Inflammation Lead to Heart Disease? Trends Cardiovasc Med. 2020;30(8):463-9. DOI:10.1016/j.tcm.2019.10.001
31. Brown AC, Rampertab SD, Mullin GE. Existing dietary guidelines for Crohn's disease and ulcerative colitis. Exp Rev Gastroenterol Hepatol. 2011;5(3):411-25. DOI:10.1586/egh.11.29
32. Singh S, Singh H, Loftus EV, Pardi DS. Risk of cerebrovascular accidents and ischemic heart disease in patients with inflammatory bowel disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12:382-93. DOI:10.1016/j.cgh.2013.08.023
33. Kristensen SL, Ahlehoff O, Lindhardsen J, et al. Disease activity in inflammatory bowel disease is associated with increased risk of myocardial infarction, stroke and cardiovascular death – a Danish nationwide cohort study [published correction appears in PLoS One. 2013;8(4).
DOI:10.1371/annotation/b4a49855-87b9-436a-a4bd-bc64b50a6c93]. PLoS One. 2013;8(2):e56944. DOI:10.1371/journal.pone.0056944
34. Sun HH, Tian F. Inflammatory bowel disease and cardiovascular disease incidence and mortality: A meta-analysis. Eur J Prev Cardiol. 2018;25(15):1623-31. DOI:10.1177/2047487318792952
35. Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med. 2008;5(4):e78. DOI:10.1371/journal.pmed.0050078
36. Wang A, Liu J, Li C, et al. Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of Cardiovascular Disease. J Am Heart Assoc. 2017;6(10):e005610. DOI:10.1161/JAHA.117.005610
37. Fadeeva NA, Korneeva IA, Knyazev OV, Parfenov AI. Biomarkers of inflammatory bowel disease activity. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(12):107-11. DOI:10.26442/00403660.2018.12.000018
38. Averill MM, Kerkhoff C, Bornfeldt KE. S100A8 and S100A9 in cardiovascular biology and disease. Arterioscler Thromb Vasc Biol. 2012;32(2):223-9. DOI:10.1161/ATVBAHA.111.236927
39. Singh S, Kullo IJ, Pardi DS, Loftus EV. Epidemiology, risk factors and management of cardiovascular diseases in IBD. Nat Rev Gastroenterol Hepatol. 2015;12(1):26-35. DOI:10.1038/nrgastro.2014.202
40. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263-82. DOI:10.1016/j.cjca.2016.07.510
41. Wu GC, Leng RX, Lu Q, et al. Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Angiology. 2017;68:447-61. DOI:10.1177/0003319716652031
42. Maharshak N, Arbel Y, Bornstein NM, et al. Inflammatory bowel disease is not associated with increased intimal media thickening. Am J Gastroenterol. 2007;102(5):1050-5. DOI:10.1111/j.1572-0241.2007.01086.x
43 Broide E, Schopan A, Zaretsky M, et al. Intima-media thickness of the common carotid artery is not significantly higher in Crohn's disease patients compared to healthy population. Dig Dis Sci. 2011;56(1):197-202.
DOI:10.1007/s10620-010-1235-0
44. Theocharidou E, Gossios TD, Griva T, et al. Is There an Association between Inflammatory Bowel Diseases and Carotid Intima-media Thickness? Preliminary Data. Angiology. 2014;65(6):543-50. DOI:10.1177/0003319713489876
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1. Kondubhatla K, Kaushal A, Daoud A, et al. Pro-Atherogenic Inflammatory Mediators in Inflammatory Bowel Disease Patients Increase the Risk of Thrombosis, Coronary Artery Disease, and Myocardial Infarction: A Scientific Dilemma. Cureus. 2020;12(9):1-10.
DOI:10.7759/cureus.10544
2. Garber A, Regueiro M. Extraintestinal Manifestations of Inflammatory Bowel Disease: Epidemiology, Etiopathogenesis, and Management. Curr Gastroenterol Rep. 2019;21(7). DOI:10.1007/s11894-019-0698-1
3. Harbord M, Annese V, Vavricka SR, et al. The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohns Colitis. 2016;10(3):239-54.
DOI:10.1093/ecco-jcc/jjv213
4. Aarestrup J, Jess T, Kobylecki CJ, et al. Cardiovascular Risk Profile Among Patients With Inflammatory Bowel Disease: A Population-based Study of More Than 100 000 Individuals. J Crohns Colitis. 2019;13(3):319-23. DOI:10.1093/ecco-jcc/jjy164.
5. Panhwar MS, Mansoor E, Al-Kindi SG, et al. Risk of Myocardial Infarction in Inflammatory Bowel Disease: A Population-based National Study. Inflamm Bowel Dis. 2019;25(6):1080-7.
DOI:10.1093/ibd/izy354
6. Czubkowski P, Osiecki M, Szymańska E, Kierkuś J. The risk of cardiovascular complications in inflammatory bowel disease. Clin Exp Med. 2020;20(4):481-91. DOI:10.1007/s10238-020-00639-y
7. Zanoli L, Mikhailidis DP, Bruno RM, et al. Aortic Stiffening Is an Extraintestinal Manifestation of Inflammatory Bowel Disease: Review of the Literature and Expert Panel Statement. Angiology. 2020;71(8):689-97. DOI:10.1177/0003319720918509
8. Bernstein CN, Blanchard JF, Houston DS. The incidence of deep venous thrombosis and pulmonary embolism among patients with infammatory bowel disease: a population-based cohort study. Thromb Haemost. 2001;85(3):430-4.
9. Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375(9715):657-63. DOI:10.1016/S0140-6736(09)61963-2
10. Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut. 2004;53(4):542-8. DOI:10.1136/gut.2003.025411
11. Pepe M, Carulli E, Forleo C, et al. Inflammatory Bowel Disease and Acute Coronary Syndromes: From Pathogenesis to the Fine Line between Bleeding and Ischemic Risk. Inflamm Bowel Dis. 2021;27(5):725-31. DOI:10.1093/ibd/izaa160
12. Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica. 2000;85(9):967-72. PMID: 10980636.
13. Stocker R, Keaney JF. New insights on oxidative stress in the artery wall. J Thromb Haemost. 2005;3(8):1825-34.
DOI:10.1111/j.1538-7836.2005.01370.x
14. Sokolova LK, Pushkarev VM, Pushkarev VV, et al. Diabetes mellitus and atherosclerosis. The role of inflammatory processes in pathogenesis (literature review). Int J Endocrinol. 2017;13(7):486-98. DOI:10.22141/2224-0721.13.7.2017.115747
15. Van Leuven SI, Hezemans R, Levels JH, et al. Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease.
J Lipid Res. 2007;48(12):2640-6. DOI:10.1194/jlr.M700176-JLR20
16. Tang WH, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017;120(7):1183-96.
DOI:10.1161/CIRCRESAHA.117.309715
17. Van der Sloot KWJ, Amini M, Peters V, et al. Inflammatory Bowel Diseases: Review of Known Environmental Protective and Risk Factors Involved. Inflamm Bowel Dis. 2017;23(9):1499-509.
DOI:10.1097/MIB.0000000000001217
18. Underwood MA. Intestinal dysbiosis: novel mechanisms by which gut microbes trigger and prevent disease. Prev Med. 2014;65:133-7. DOI:10.1016/j.ypmed.2014.05.010
19. Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol.
2013;13(5):321-35. DOI:10.1038/nri3430
20. Lorenz RG, Chaplin DD, McDonald KG, et al. Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin beta receptor, and TNF receptor I function. J Immunol. 2003;170(11):5475-82.
DOI:10.4049/jimmunol.170.11.5475
21. Diehl GE, Longman RS, Zhang JX, et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature. 2013;494(7435):116-20. DOI:10.1038/nature11809
22. Wrzosek L, Miquel S, Noordine ML, et al. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 2013;11:61.
DOI:10.1186/1741-7007-11-61
23. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol. 2017;14(10):573-84. DOI:10.1038/nrgastro.2017.88
24. Biedermann L, Fournier N, Misselwitz B, et al. High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation – Data from the Swiss IBD Cohort Study [published correction appears in J Crohns Colitis. 2016 Jun;10(6):754]. J Crohns Colitis. 2015;9(10):819-29. DOI:10.1093/ecco-jcc/jjv113
25. Bastida G, Beltrán B. Ulcerative colitis in smokers, non-smokers and ex-smokers. World J Gastroenterol. 2011;17(22):2740-7.
DOI:10.3748/wjg.v17.i22.2740
26. Biondi RB, Salmazo PS, Bazan SGZ, et al. Cardiovascular risk in individuals with inflammatory bowel disease. Clin Exp Gastroenterol. 2020;13:107-13. DOI:10.2147/CEG.S243478
27. Cappello M, Licata A, Calvaruso V, et al. Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease. Eur J Intern Med. 2017;37:83-9. DOI:10.1016/j.ejim.2016.10.004
28. Kakodkar S, Mutlu EA. Diet as a Therapeutic Option for Adult Inflammatory Bowel Disease. Gastroenterol Clin North Am. 2017;46(4):745-67. DOI:10.1016/j.gtc.2017.08.016
29. Shon WJ, Jung MH, Choi EY, Shin DM. Sugar-sweetened Beverage and High Fat Diet Consumption Harmfully Alters Gut Microbiota and Promotes Gut Inflammation
(P20-041-19). Curr Dev Nutr. 2019;3(Suppl. 1):nzz040.P20-041-19.
DOI:10.1093/cdn/nzz040.P20-041-19
30. Bigeh A, Sanchez A, Maestas C, Gulati M. Inflammatory Bowel Disease & The Risk for Cardiovascular Disease: Does All Inflammation Lead to Heart Disease? Trends Cardiovasc Med. 2020;30(8):463-9. DOI:10.1016/j.tcm.2019.10.001
31. Brown AC, Rampertab SD, Mullin GE. Existing dietary guidelines for Crohn's disease and ulcerative colitis. Exp Rev Gastroenterol Hepatol. 2011;5(3):411-25. DOI:10.1586/egh.11.29
32. Singh S, Singh H, Loftus EV, Pardi DS. Risk of cerebrovascular accidents and ischemic heart disease in patients with inflammatory bowel disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2014;12:382-93. DOI:10.1016/j.cgh.2013.08.023
33. Kristensen SL, Ahlehoff O, Lindhardsen J, et al. Disease activity in inflammatory bowel disease is associated with increased risk of myocardial infarction, stroke and cardiovascular death – a Danish nationwide cohort study [published correction appears in PLoS One. 2013;8(4).
DOI:10.1371/annotation/b4a49855-87b9-436a-a4bd-bc64b50a6c93]. PLoS One. 2013;8(2):e56944. DOI:10.1371/journal.pone.0056944
34. Sun HH, Tian F. Inflammatory bowel disease and cardiovascular disease incidence and mortality: A meta-analysis. Eur J Prev Cardiol. 2018;25(15):1623-31. DOI:10.1177/2047487318792952
35. Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med. 2008;5(4):e78. DOI:10.1371/journal.pmed.0050078
36. Wang A, Liu J, Li C, et al. Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of Cardiovascular Disease. J Am Heart Assoc. 2017;6(10):e005610. DOI:10.1161/JAHA.117.005610
37. Fadeeva NA, Korneeva IA, Knyazev OV, Parfenov AI. Biomarkers of inflammatory bowel disease activity. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(12):107-11. DOI:10.26442/00403660.2018.12.000018
38. Averill MM, Kerkhoff C, Bornfeldt KE. S100A8 and S100A9 in cardiovascular biology and disease. Arterioscler Thromb Vasc Biol. 2012;32(2):223-9. DOI:10.1161/ATVBAHA.111.236927
39. Singh S, Kullo IJ, Pardi DS, Loftus EV. Epidemiology, risk factors and management of cardiovascular diseases in IBD. Nat Rev Gastroenterol Hepatol. 2015;12(1):26-35. DOI:10.1038/nrgastro.2014.202
40. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263-82. DOI:10.1016/j.cjca.2016.07.510
41. Wu GC, Leng RX, Lu Q, et al. Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Angiology. 2017;68:447-61. DOI:10.1177/0003319716652031
42. Maharshak N, Arbel Y, Bornstein NM, et al. Inflammatory bowel disease is not associated with increased intimal media thickening. Am J Gastroenterol. 2007;102(5):1050-5. DOI:10.1111/j.1572-0241.2007.01086.x
43 Broide E, Schopan A, Zaretsky M, et al. Intima-media thickness of the common carotid artery is not significantly higher in Crohn's disease patients compared to healthy population. Dig Dis Sci. 2011;56(1):197-202.
DOI:10.1007/s10620-010-1235-0
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Авторы
О.Ю. Миронова*, М.А. Исайкина, С.А. Хасиева
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*mironova_o_yu@staff.sechenov.ru
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Olga Iu. Mironova*, Mariia A. Isaikina, Sofiia A. Khasieva