nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-207-11-36-45nogr-2187Research ArticleМИКРОБИОЦЕНОЗЫMICROBIOCENOSESНарушение кишечной проницаемости и ее роль в развитии сердечно-сосудистых осложнений у лиц с воспалительными заболеваниями кишечникаDisturbance of intestinal permeability and its role in the development of cardiovascular complications in persons with inflammatory bowel diseaseshttps://orcid.org/0000-0003-4860-0112ХлыноваО. В.KhlynovaO. V.olgakhlynova@mail.ruhttps://orcid.org/0000-0002-6176-4026СтепинаЕ. А.StepinaE. A.noemail@neicon.ruФГБОУ ВО «Пермский государственный медицинский университет им. академика Е. А. Вагнера» Минздрава РоссииРоссияPerm state medical University named after academician E. A. Wagner of Ministry of healthcare of the Russian FederationRussian Federation2022230120230113645Copyright © Хлынова О.В., Степина Е.А., 20232023Хлынова О.В., Степина Е.А.Khlynova O.V., Stepina E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/2187

Воспалительные заболевания кишечника (ВЗК) представляют собой одну из наиболее сложных и значимых проблем современной гастроэнтерологии. Неуклонный рост заболеваемости, сложные патогенетические механизмы развития, наличие тяжелых внекишечных проявлений и осложнений делают эту проблем социально значимой. В статье представлены современные взгляды на некоторые аспекты патогенеза ВЗК. В настоящее время ключевыми звеньями в развитии и прогрессировании ВЗК, а также в формирование ассоциированных сердечно-сосудистых заболеваний (АССЗ) являются состояние кишечной микробиоты и уровень эндотоксемии. Определена роль N-оксида триметиламина ТМАО, как фактора раннего развития атеросклероза, у пациентов с ВЗК.

Inflammatory bowel diseases (IBD) are one of the most complex and significant problems of modern gastroenterology. The steady increase in morbidity, complex pathogenetic mechanisms of development, the presence of severe extra-intestinal manifestations and complications make this problem socially significant. The article presents modern views on some aspects of the pathogenesis of IBD. Currently, the key links in the development and progression of IBD, as well as the development of associated cardiovascular diseases are the state of the intestinal microbiota and the level of endotoxemia. The role of trimethylamine N-oxide as a factor in the early development of atherosclerosis in patients with IBD was determined.

воспалительные заболевания кишечника (ВЗК)язвенный колит (ЯК)болезнь Крона (БК)микробиотаэндотоксинN-оксид триметиламин (ТМАО)сердечно-сосудистые заболевания (ССЗ)inflammatory bowel diseases (IBD)ulcerative colitis (UC)Crohn’s disease (CD)microbiotaendotoxintrimethylamine N-oxidecardiovascular diseasesReferencesGuan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res. 2019;2019:72472382019. doi: 10.1155/2019/7247238Guan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res. 2019;2019:72472382019. doi: 10.1155/2019/7247238Ng S.C., Shi H. Y., Hamidi N. et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018;390(10114): 2769-2778. doi: 10.1016/S0140-6736(17)32448-0Ng S.C., Shi H. Y., Hamidi N. et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018;390(10114): 2769-2778. doi: 10.1016/S0140-6736(17)32448-0Molodecky N.A., Soon I. S., Rabi D. M. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46-54. doi: 10.1053/j.gastro.2011.10.001Molodecky N.A., Soon I. S., Rabi D. M. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46-54. doi: 10.1053/j.gastro.2011.10.001Belousova E. A. Epidemiology of inflammatory bowel disease in Russia. Falk Symposium. 2006: 31.Belousova E. A. Epidemiology of inflammatory bowel disease in Russia. Falk Symposium. 2006: 31.Knyazev O.V., Shkurko T. V., Fadeyeva N. A., Bakulin I. G., Bordin D. S. Epidemiology of chronic inflammatory bowel disease. Yesterday, today, romorrow. Experimental and Clinical Gastroenterology. 2017;(3):4-12. (In Russ.)@@ Князев О. В., Шкурко Т. В., Фадеева Н. А., Бакулин И. Г., Бордин Д. С. Эпидемиология хронических воспалительных заболеваний кишечника. Вчера, сегодня, завтра. Экспериментальная и клиническая гастроэнтерология. 2017;139(3): 4-12.Knyazev O.V., Shkurko T. V., Fadeyeva N. A., Bakulin I. G., Bordin D. S. Epidemiology of chronic inflammatory bowel disease. Yesterday, today, romorrow. Experimental and Clinical Gastroenterology. 2017;(3):4-12. (In Russ.)@@ Князев О. В., Шкурко Т. В., Фадеева Н. А., Бакулин И. Г., Бордин Д. С. Эпидемиология хронических воспалительных заболеваний кишечника. Вчера, сегодня, завтра. Экспериментальная и клиническая гастроэнтерология. 2017;139(3): 4-12.Khor B., Gardet A., Xavier R. J. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351): 307-317. doi: 10.1038/nature10209Khor B., Gardet A., Xavier R. J. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351): 307-317. doi: 10.1038/nature10209Kaser A., Zeissig S., Blumberg R. S. Inflammatory bowel disease. Annual Review of Immunology. 2010;28: 573-621. doi: 10.1146/annurev-immunol-030409-101225Kaser A., Zeissig S., Blumberg R. S. Inflammatory bowel disease. Annual Review of Immunology. 2010;28: 573-621. doi: 10.1146/annurev-immunol-030409-101225Peters L.A., Perrigoue J., Mortha A. et al. A functional genomics predictive network model identifies regulators of inflammatory bowel disease. Nature Genetics. 2017;49(10): 1437-1449. doi: 10.1038/ng.3947Peters L.A., Perrigoue J., Mortha A. et al. A functional genomics predictive network model identifies regulators of inflammatory bowel disease. Nature Genetics. 2017;49(10): 1437-1449. doi: 10.1038/ng.3947Coskun M.Intestinal epithelium in inflammatory bowel disease. Frontiers in Medicine. 2014;1:24. doi: 10.3389/fmed.2014.00024.Coskun M.Intestinal epithelium in inflammatory bowel disease. Frontiers in Medicine. 2014;1:24. doi: 10.3389/fmed.2014.00024.Nishida A., Inoue R., Inatomi O. et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Journal of Clinical Gastroenterology. 2018; 11(1):1-10. doi: 10.1007/s12328-017-0813-5Nishida A., Inoue R., Inatomi O. et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Journal of Clinical Gastroenterology. 2018; 11(1):1-10. doi: 10.1007/s12328-017-0813-5Fritz J.V., Desai M. S., Shah P., Schneider J. G., Wilmes P. From meta-omics to causality: Experimental models for human microbiome research. Microbiome. 2013;1(1):14. doi: 10.1186/2049-2618-1-14.Fritz J.V., Desai M. S., Shah P., Schneider J. G., Wilmes P. From meta-omics to causality: Experimental models for human microbiome research. Microbiome. 2013;1(1):14. doi: 10.1186/2049-2618-1-14.Antoni L., Nuding S., Wehkamp J., Stange E. F.Intestinal barrier in inflammatory bowel disease. World Journal of Gastroenterology. 2014;20(5):1165-1179. doi: 10.3748/wjg.v20.i5.1165Antoni L., Nuding S., Wehkamp J., Stange E. F.Intestinal barrier in inflammatory bowel disease. World Journal of Gastroenterology. 2014;20(5):1165-1179. doi: 10.3748/wjg.v20.i5.1165Jager S., Stange E. F., Wehkamp J. Inflammatory bowel disease: an impaired barrier disease. Langenbeck’s Archives of Surgery. 2013; 398(1):1-12. doi: 10.1007/s00423-012-1030-9Jager S., Stange E. F., Wehkamp J. Inflammatory bowel disease: an impaired barrier disease. Langenbeck’s Archives of Surgery. 2013; 398(1):1-12. doi: 10.1007/s00423-012-1030-9Teshima W., Dieleman L. A., Meddings J. B. Abnormal intestinal permeability in Crohn’s disease pathogenesis. Annals of the New York Academy of Sciences. 2012;1258:159-165. doi: 10.1111/j.1749-6632.2012.06612.xTeshima W., Dieleman L. A., Meddings J. B. Abnormal intestinal permeability in Crohn’s disease pathogenesis. Annals of the New York Academy of Sciences. 2012;1258:159-165. doi: 10.1111/j.1749-6632.2012.06612.xVivinus-Nebot M., Frin-Mathy G., Bzioueche H. et al. Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut. 2014; 63(5):744-752. doi: 10.1136/gutjnl-2012-304066Vivinus-Nebot M., Frin-Mathy G., Bzioueche H. et al. Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut. 2014; 63(5):744-752. doi: 10.1136/gutjnl-2012-304066Zeissig S., Bürgel N., Günzel D. et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut. 2007; 56(1): 61-72. doi: 10.1136/gut.2006.094375Zeissig S., Bürgel N., Günzel D. et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut. 2007; 56(1): 61-72. doi: 10.1136/gut.2006.094375Fries W., Renda M. C., Lo Presti M. A. et al.Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn’s disease in Southern Italy. The American Journal of Gastroenterology. 2005;100(12): 2730-2736. doi: 10.1111/j.1572-0241.2005.00325.xFries W., Renda M. C., Lo Presti M. A. et al.Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn’s disease in Southern Italy. The American Journal of Gastroenterology. 2005;100(12): 2730-2736. doi: 10.1111/j.1572-0241.2005.00325.xBuhner S., Buning C., Genschel J. et al. Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of CARD15 3020insC mutation? Gut. 2006; 55(3): 342-347. doi: 10.1136/gut.2005.065557Buhner S., Buning C., Genschel J. et al. Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of CARD15 3020insC mutation? Gut. 2006; 55(3): 342-347. doi: 10.1136/gut.2005.065557Bamias G., Nyce M. R., De La Rue S. A., Cominelli F. New concepts in the pathophysiology of inflammatory bowel disease. Annals of Internal Medicine. 2005; 143(12): 895-904. doi: 10.7326/0003-4819-143-12-200512200-00007Bamias G., Nyce M. R., De La Rue S. A., Cominelli F. New concepts in the pathophysiology of inflammatory bowel disease. Annals of Internal Medicine. 2005; 143(12): 895-904. doi: 10.7326/0003-4819-143-12-200512200-00007Strober W., Watanabe T. NOD2, an intracellular innate immune sensor involved in host defense and Crohn’s disease. Mucosal Immunology. 2011; 4(5):484-495. doi: 0.1038/mi.2011.29.Strober W., Watanabe T. NOD2, an intracellular innate immune sensor involved in host defense and Crohn’s disease. Mucosal Immunology. 2011; 4(5):484-495. doi: 0.1038/mi.2011.29.Kevans D., Turpin W., Madsen K. et al. Determinants of intestinal permeability in healthy first-degree relatives of individuals with Crohn’s disease. Inflammatory Bowel Diseases. 2015;21(4):879-887. doi: 10.1097/MIB.0000000000000323Kevans D., Turpin W., Madsen K. et al. Determinants of intestinal permeability in healthy first-degree relatives of individuals with Crohn’s disease. Inflammatory Bowel Diseases. 2015;21(4):879-887. doi: 10.1097/MIB.0000000000000323Rehman A., Sina C., Gavrilova O. et al. Nod2 is essential for temporal development of intestinal microbial communities. Gut. 2011;60(10): 1354-1362. doi: 10.1136/gut.2010.216259Rehman A., Sina C., Gavrilova O. et al. Nod2 is essential for temporal development of intestinal microbial communities. Gut. 2011;60(10): 1354-1362. doi: 10.1136/gut.2010.216259Fava F., Danese S.Intestinal microbiota in inflammatory bowel disease: friend of foe? World Journal of Gastroenterology. 2011;17(5):557-566, doi: 10.3748/wjg.v17.i5.557Fava F., Danese S.Intestinal microbiota in inflammatory bowel disease: friend of foe? World Journal of Gastroenterology. 2011;17(5):557-566, doi: 10.3748/wjg.v17.i5.557Chelakkot C., Ghim J., Ryu S. H. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 2018;50(8):1-9. doi: 10.1038/s12276-018-0126-xChelakkot C., Ghim J., Ryu S. H. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 2018;50(8):1-9. doi: 10.1038/s12276-018-0126-xSmyth D., Phan V., Wang A., McKay D.M.Interferon-γ-induced increases in intestinal epithelial macromolecular permeability requires the Src kinase Fyn. Lab Investig.2011;91(5):764-777. doi: 10.1038/labinvest.2010.208Smyth D., Phan V., Wang A., McKay D.M.Interferon-γ-induced increases in intestinal epithelial macromolecular permeability requires the Src kinase Fyn. Lab Investig.2011;91(5):764-777. doi: 10.1038/labinvest.2010.208Schultz C. Lipopolysaccharide, structure and biological effects. Gen Intern Med Clin Innov. 2018;3:1-2. doi: 10.15761/GIMCI.1000152Schultz C. Lipopolysaccharide, structure and biological effects. Gen Intern Med Clin Innov. 2018;3:1-2. doi: 10.15761/GIMCI.1000152Kim S., Patel D. S., Park S., Slusky J., Klauda J. B., Widmalm G. et al. Bilayer Properties of Lipid A from Various Gram-Negative Bacteria. Biophys J. 2016;111(8):1750-1760. doi: 10.1016/j.bpj.2016.09.001.Kim S., Patel D. S., Park S., Slusky J., Klauda J. B., Widmalm G. et al. Bilayer Properties of Lipid A from Various Gram-Negative Bacteria. Biophys J. 2016;111(8):1750-1760. doi: 10.1016/j.bpj.2016.09.001.Rhee S. H. Lipopolysaccharide: Basic Biochemistry, Intracellular Signaling, and Physiological Impacts in the Gut.Intest Res. 2014;12(2):90-95. doi: 10.5217/ir.2014.12.2.90Rhee S. H. Lipopolysaccharide: Basic Biochemistry, Intracellular Signaling, and Physiological Impacts in the Gut.Intest Res. 2014;12(2):90-95. doi: 10.5217/ir.2014.12.2.90Jang J.H., Shin H. W., Lee J. M., Lee H. W., Kim E. C., Park S. H. An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp. Mediators Inflamm. 2015;2015:794143. doi: 10.1155/2015/794143Jang J.H., Shin H. W., Lee J. M., Lee H. W., Kim E. C., Park S. H. An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp. Mediators Inflamm. 2015;2015:794143. doi: 10.1155/2015/794143Mogensen T. H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240-273. doi: 10.1128/CMR.00046-08Mogensen T. H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240-273. doi: 10.1128/CMR.00046-08Kawasaki T., Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014; 5:461. doi: 10.3389/fimmu.2014.00461Kawasaki T., Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014; 5:461. doi: 10.3389/fimmu.2014.00461Koeth R. A., Levison B. S., Culley M. K. et al. γ-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metabolism. 2014;20(5):799-812. doi: 10.1016/j.cmet.2014.10.006Koeth R. A., Levison B. S., Culley M. K. et al. γ-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metabolism. 2014;20(5):799-812. doi: 10.1016/j.cmet.2014.10.006Yancey P. H. Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. Journal of Experimental Biology. 2005;208(Pt 15):2819-2830. doi: 10.1242/jeb.01730Yancey P. H. Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. Journal of Experimental Biology. 2005;208(Pt 15):2819-2830. doi: 10.1242/jeb.01730Zeisel S.H., da Costa K. A. Choline: an essential nutrient for public health. Nutrition Reviews. 2009;67(11):615-623. doi: 10.1111/j.1753-4887.2009.00246.xZeisel S.H., da Costa K. A. Choline: an essential nutrient for public health. Nutrition Reviews. 2009;67(11):615-623. doi: 10.1111/j.1753-4887.2009.00246.xTang W. H., Wang Z., Levison B. S., et al.Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. The New England Journal of Medicine. 2013;368(17):1575-1584. doi: 10.1056/NEJMoa1109400Tang W. H., Wang Z., Levison B. S., et al.Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. The New England Journal of Medicine. 2013;368(17):1575-1584. doi: 10.1056/NEJMoa1109400Brown J. M., Hazen S. L. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annual Review of Medicine. 2015;66(1):343-359. doi: 10.1146/annurev-med-060513-093205.Brown J. M., Hazen S. L. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annual Review of Medicine. 2015;66(1):343-359. doi: 10.1146/annurev-med-060513-093205.Zhu W., Gregory J. C., Org E. et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111-124. doi: 10.1016/j.cell.2016.02.011Zhu W., Gregory J. C., Org E. et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111-124. doi: 10.1016/j.cell.2016.02.011Romano K. A., Vivas E. I., Amador-Noguez D., Rey F. E.Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio. 2015;6(2): e02481. doi: 10.1128/mBio.02481-14.Romano K. A., Vivas E. I., Amador-Noguez D., Rey F. E.Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. mBio. 2015;6(2): e02481. doi: 10.1128/mBio.02481-14.Geng J., Yang C., WangВ., Zhang X. et al. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed Pharmacother. 2018;97:941-947. doi: 10.1016/j.biopha.2017.11.016Geng J., Yang C., WangВ., Zhang X. et al. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed Pharmacother. 2018;97:941-947. doi: 10.1016/j.biopha.2017.11.016Liu Y., Dai M. Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis.Mediators Inflamm. 2020; 2020:4634172. doi: 10.1155/2020/4634172.Liu Y., Dai M. Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis.Mediators Inflamm. 2020; 2020:4634172. doi: 10.1155/2020/4634172.Seldin M. M., Meng Y., Qi H. et al. Trimethylamine N-Oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear Factor-κB. Journal of the American Heart Association. 2016;5(2): e002767. doi: 10.1161/JAHA.115.002767.Seldin M. M., Meng Y., Qi H. et al. Trimethylamine N-Oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear Factor-κB. Journal of the American Heart Association. 2016;5(2): e002767. doi: 10.1161/JAHA.115.002767.Li T., Chen Y., Gua C., Li X. Elevated circulating trimethylamine N-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Frontiers in Physiology. 2017;8:350. doi: 10.3389/fphys.2017.00350Li T., Chen Y., Gua C., Li X. Elevated circulating trimethylamine N-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Frontiers in Physiology. 2017;8:350. doi: 10.3389/fphys.2017.00350Mafune A., Iwamoto T., Tsutsumi Y. et al. Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study. Clinical and Experimental Nephrology. 2016;20(5):731-739. doi: 10.1007/s10157-015-1207-yMafune A., Iwamoto T., Tsutsumi Y. et al. Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study. Clinical and Experimental Nephrology. 2016;20(5):731-739. doi: 10.1007/s10157-015-1207-ySenthong V., Wang Z., Li X. S. et al.Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. Journal of the American Heart Association. 2016;5(6): e002816. doi: 10.1161/JAHA.115.002816Senthong V., Wang Z., Li X. S. et al.Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. Journal of the American Heart Association. 2016;5(6): e002816. doi: 10.1161/JAHA.115.002816Ke Y., Li D., Zhao M. et al. Gut flora-dependent metabolite trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radical Biology and Medicine. 2018;116:88-100. doi: 10.1016/j.freeradbiomed.2018.01.007Ke Y., Li D., Zhao M. et al. Gut flora-dependent metabolite trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radical Biology and Medicine. 2018;116:88-100. doi: 10.1016/j.freeradbiomed.2018.01.007Hansson G. K. Inflammation, atherosclerosis, and coronary artery disease N Engl J Med. 2005;352(16):1685-1695. doi: 0.1056/NEJMra043430Hansson G. K. Inflammation, atherosclerosis, and coronary artery disease N Engl J Med. 2005;352(16):1685-1695. doi: 0.1056/NEJMra043430Lindhardsen J., Ahlehoff O., Gislason G. H., Madsen O. R. et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011;70(6):929-934. doi: 10.1136/ard.2010.143396Lindhardsen J., Ahlehoff O., Gislason G. H., Madsen O. R. et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011;70(6):929-934. doi: 10.1136/ard.2010.143396Kim D., Zeng M. Y., Nunez G. The interplay between host immune cells and gut microbiota in chronic inflammatory diseases. Exp. Mol. Med. 2017;49(5): e339. doi: 10.1038/emm.2017.24.Kim D., Zeng M. Y., Nunez G. The interplay between host immune cells and gut microbiota in chronic inflammatory diseases. Exp. Mol. Med. 2017;49(5): e339. doi: 10.1038/emm.2017.24.Steinbach E.C., Plevy S. E. The role of macrophages and dendritic cells in the initiation of inflammation in IBD. Inflamm Bowel Dis. 2014;20(1):166-175. doi: 10.1097/MIB.0b013e3182a69dca.Steinbach E.C., Plevy S. E. The role of macrophages and dendritic cells in the initiation of inflammation in IBD. Inflamm Bowel Dis. 2014;20(1):166-175. doi: 10.1097/MIB.0b013e3182a69dca.Denning T. L., Wang Y. C., Patel S. R., Williams I. R., Pulendran B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol. 2007;8(10):1086-1094. doi: 10.1038/ni1511Denning T. L., Wang Y. C., Patel S. R., Williams I. R., Pulendran B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol. 2007;8(10):1086-1094. doi: 10.1038/ni1511Boyapati R., Satsangi J., Ho G. T. Pathogenesis of Crohn’s disease. F1000Prime Rep. 2015;7:44. doi: 10.12703/P7-44Boyapati R., Satsangi J., Ho G. T. Pathogenesis of Crohn’s disease. F1000Prime Rep. 2015;7:44. doi: 10.12703/P7-44Bradford K., Shih D. Q. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease. World J Gastroenterol. 2011;17(37):4166-4173. doi: 10.3748/wjg.v17.i37.4166Bradford K., Shih D. Q. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease. World J Gastroenterol. 2011;17(37):4166-4173. doi: 10.3748/wjg.v17.i37.4166Poon S.S., Asher R., Jackson R., Kneebone A., Collins P. et al. Body mass index and smoking affect thioguanine nucleotide levels in inflammatory bowel disease. J Crohns Colitis. 2015;9(8): 640-646. doi: 10.1093/ecco-jcc/jjv084Poon S.S., Asher R., Jackson R., Kneebone A., Collins P. et al. Body mass index and smoking affect thioguanine nucleotide levels in inflammatory bowel disease. J Crohns Colitis. 2015;9(8): 640-646. doi: 10.1093/ecco-jcc/jjv084Panhwar M. S., Mansoor E., Al-Kindi S.G., Sinh P., Katz J. et al. Risk of Myocardial Infarction in Inflammatory Bowel Disease: A Population-based National Study. Inflammatory Bowel Diseases. 2019; 25(6):1080-1087. doi: 10.1093/ibd/izy354Panhwar M. S., Mansoor E., Al-Kindi S.G., Sinh P., Katz J. et al. Risk of Myocardial Infarction in Inflammatory Bowel Disease: A Population-based National Study. Inflammatory Bowel Diseases. 2019; 25(6):1080-1087. doi: 10.1093/ibd/izy354Kirchgesner J., Beaugerie L., Carrat F., Nyboe Andersen N., Jess T., Schwarzinger M. Increased risk of acute arterial events in young patients with severely active inflammatory bowel disease: a nationwide French cohort study. Gut. 2018;67(7):1261-1268. doi: 10.1136/gutjnl-2017-314015Kirchgesner J., Beaugerie L., Carrat F., Nyboe Andersen N., Jess T., Schwarzinger M. Increased risk of acute arterial events in young patients with severely active inflammatory bowel disease: a nationwide French cohort study. Gut. 2018;67(7):1261-1268. doi: 10.1136/gutjnl-2017-314015Owczarek D., Cibor D., Glowacki M. K., Rodacki T., Mach T. Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability. World J. Gastroenterol. 2014;20(1):53-63. doi: 10.3748/wjg.v20.i1.53Owczarek D., Cibor D., Glowacki M. K., Rodacki T., Mach T. Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability. World J. Gastroenterol. 2014;20(1):53-63. doi: 10.3748/wjg.v20.i1.53Aniwan S., Park S. H., Loftus E. V. Epidemiology, natural history, and risk stratification of Crohn’s disease. Gastroenterol Clin North Am. 2017;46 (3): 463-480. doi: 10.1016/j.gtc.2017.05.003Aniwan S., Park S. H., Loftus E. V. Epidemiology, natural history, and risk stratification of Crohn’s disease. Gastroenterol Clin North Am. 2017;46 (3): 463-480. doi: 10.1016/j.gtc.2017.05.003Panhwar M. S., Mansoor E., Al-Kindi S.G., Sinh P., Katz J., Oliveira G. H. et al. Risk of myocardial infarction in inflammatory bowel disease: a population-based national study. Inflamm Bowel Dis.2019;25(6):1080-1087. doi: 10.1093/ibd/izy354Panhwar M. S., Mansoor E., Al-Kindi S.G., Sinh P., Katz J., Oliveira G. H. et al. Risk of myocardial infarction in inflammatory bowel disease: a population-based national study. Inflamm Bowel Dis.2019;25(6):1080-1087. doi: 10.1093/ibd/izy354Feng W., Chen G., Cai D., Zhao S., Cheng J., Shen H. Inflammatory bowel disease and risk of ischemic heart disease: an updated meta-analysis of cohort studies. J Am Heart Assoc.2017;6(8): e005892. doi: 10.1161/JAHA.117.005892Feng W., Chen G., Cai D., Zhao S., Cheng J., Shen H. Inflammatory bowel disease and risk of ischemic heart disease: an updated meta-analysis of cohort studies. J Am Heart Assoc.2017;6(8): e005892. doi: 10.1161/JAHA.117.005892Genkel V. V., Shaposhnik I. I. Inflammatory Bowel Disease and Statins.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(1):7-13. (In Russ.) doi: 10.22416/1382-4376-2020-30-1-7-13@@ Генкель В. В., Шапошник И. И. Воспалительные заболевания кишечника и статины. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(1):7-13.Genkel V. V., Shaposhnik I. I. Inflammatory Bowel Disease and Statins.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(1):7-13. (In Russ.) doi: 10.22416/1382-4376-2020-30-1-7-13@@ Генкель В. В., Шапошник И. И. Воспалительные заболевания кишечника и статины. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(1):7-13.Bereswill S., Muñoz M., Fischer A., et al. Anti-inflammatory effects of Resveratrol, Curcumin and simvastatin in acute small intestinal inflammation. PLoS One. 2010;5(12): e15099. doi: 10.1371/journal.pone.0015099Bereswill S., Muñoz M., Fischer A., et al. Anti-inflammatory effects of Resveratrol, Curcumin and simvastatin in acute small intestinal inflammation. PLoS One. 2010;5(12): e15099. doi: 10.1371/journal.pone.0015099Grip O., Janciauskiene S., Bredberg A. Use of atorvastatin as an anti-inflammatory treatment in Crohn’s disease. Br J Pharmacol. 2008;155(7):1085-1092. doi: 10.1038/bjp.2008.369Grip O., Janciauskiene S., Bredberg A. Use of atorvastatin as an anti-inflammatory treatment in Crohn’s disease. Br J Pharmacol. 2008;155(7):1085-1092. doi: 10.1038/bjp.2008.369Osterman M.T., Yang Y. X., Brensinger C., Forde K. A., Lichtenstein G. R., Lewis J. D. No increased risk of myocardial infarction among patients with ulcerative colitis or Crohn’s disease. Clin Gastroenterol Hepatol. 2011;9(10):875-880. doi: 10.1016/j.cgh.2011.06.032Osterman M.T., Yang Y. X., Brensinger C., Forde K. A., Lichtenstein G. R., Lewis J. D. No increased risk of myocardial infarction among patients with ulcerative colitis or Crohn’s disease. Clin Gastroenterol Hepatol. 2011;9(10):875-880. doi: 10.1016/j.cgh.2011.06.032Ruisi P., Makaryus J. N., Ruisi M., Makaryus A. N. Inflammatory bowel disease as a risk factor for premature coronary artery disease. J Clin Med Res. 2015;7(4):257-261. doi: 10.14740/jocmr2102wRuisi P., Makaryus J. N., Ruisi M., Makaryus A. N. Inflammatory bowel disease as a risk factor for premature coronary artery disease. J Clin Med Res. 2015;7(4):257-261. doi: 10.14740/jocmr2102wBarnes E. L., Beery R. M., Schulman A. R., McCarthy E.P., Korzenik J. R., Winter R. W. Hospitalizations for acute myocardial infarction are decreased among patients with inflammatory bowel disease using a nationwide inpatient database. Inflamm Bowel Dis. 2016;22 (9): 2229-2237. doi: 10.1097/MIB.0000000000000899Barnes E. L., Beery R. M., Schulman A. R., McCarthy E.P., Korzenik J. R., Winter R. W. Hospitalizations for acute myocardial infarction are decreased among patients with inflammatory bowel disease using a nationwide inpatient database. Inflamm Bowel Dis. 2016;22 (9): 2229-2237. doi: 10.1097/MIB.0000000000000899Ehrenpreis E. D., Zhou Y., Alexoff A., Melitas C. Effect of the diagnosis of inflammatory bowel disease on risk-adjusted mortality in hospitalized patients with acute myocardial infarction, congestive heart failure and pneumonia. PLoS One. 2016;11(7): e0158926. doi: 10.1371/journal.pone.0158926Ehrenpreis E. D., Zhou Y., Alexoff A., Melitas C. Effect of the diagnosis of inflammatory bowel disease on risk-adjusted mortality in hospitalized patients with acute myocardial infarction, congestive heart failure and pneumonia. PLoS One. 2016;11(7): e0158926. doi: 10.1371/journal.pone.0158926Sridhar A. R.M., Parasa S., Navaneethan U., Crowell, Olden K.Comprehensive study of cardiovascular morbidity in hospitalized inflammatory bowel disease patients. J Crohn’s Colitis. 2011;5(4):287-294. doi: 10.1016/j.crohns.2011.01.011Sridhar A. R.M., Parasa S., Navaneethan U., Crowell, Olden K.Comprehensive study of cardiovascular morbidity in hospitalized inflammatory bowel disease patients. J Crohn’s Colitis. 2011;5(4):287-294. doi: 10.1016/j.crohns.2011.01.011Agouridis A. P., Elisaf M., Milionis H. J. An overview of lipid abnormalities in patients with inflammatory bowel disease. Ann Gastroenterol. 2011;24(3):181-187.Agouridis A. P., Elisaf M., Milionis H. J. An overview of lipid abnormalities in patients with inflammatory bowel disease. Ann Gastroenterol. 2011;24(3):181-187.Romanato G., Scarpa M., Angriman I., Faggian D. et al. Plasma lipids and inflammation in active inflammatory bowel diseases. Aliment Pharmacol Ther. 2009;29(3):298-307. doi: 10.1111/j.1365-2036.2008.03886.xRomanato G., Scarpa M., Angriman I., Faggian D. et al. Plasma lipids and inflammation in active inflammatory bowel diseases. Aliment Pharmacol Ther. 2009;29(3):298-307. doi: 10.1111/j.1365-2036.2008.03886.xDagli N., Poyrazoglu O. K., Dagli A. F., Sahbaz F., Karaca I., Kobat M. A. et al. Is inflammatory bowel disease a risk factor for early atherosclerosis? Angiology. 2010;61(2):198-204. doi: 0.1177/0003319709333869Dagli N., Poyrazoglu O. K., Dagli A. F., Sahbaz F., Karaca I., Kobat M. A. et al. Is inflammatory bowel disease a risk factor for early atherosclerosis? Angiology. 2010;61(2):198-204. doi: 0.1177/0003319709333869Geerling B. J., Badart-Smook A., Stockbrugger R. W., Brummer R. J.Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls. Eur J Clin Nutr. 2000;54(6):514-521. doi: 10.1038/sj.ejcn.1601049Geerling B. J., Badart-Smook A., Stockbrugger R. W., Brummer R. J.Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls. Eur J Clin Nutr. 2000;54(6):514-521. doi: 10.1038/sj.ejcn.1601049Khalili H., Ananthakrishnan A. N., Konijeti G. G., Higuchi L. M. et al. Measures of obesity and risk of Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2015;21(2): 361-368. doi: 10.1097/MIB.0000000000000283Khalili H., Ananthakrishnan A. N., Konijeti G. G., Higuchi L. M. et al. Measures of obesity and risk of Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2015;21(2): 361-368. doi: 10.1097/MIB.0000000000000283Harper J. W., Sinanan M. N., Zisman T. L. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(10):2118-2124. doi: 10.1097/MIB.0b013e31829cf401Harper J. W., Sinanan M. N., Zisman T. L. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(10):2118-2124. doi: 10.1097/MIB.0b013e31829cf401Halling M. L., Kjeldsen J., Knudsen T., Nielsen J., Hansen L. K. Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases. World J Gastroenterol. 2017;23(33):6137-6146. doi: 10.3748/wjg.v23.i33.6137.Halling M. L., Kjeldsen J., Knudsen T., Nielsen J., Hansen L. K. Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases. World J Gastroenterol. 2017;23(33):6137-6146. doi: 10.3748/wjg.v23.i33.6137.Kappelman M. D., Galanko J. A., Porter C. Q., Sandler R. S. Association of paediatric inflammatory bowel disease with other immune-mediated diseases. Arch Dis Child. 2011;96(11):1042-1046.Kappelman M. D., Galanko J. A., Porter C. Q., Sandler R. S. Association of paediatric inflammatory bowel disease with other immune-mediated diseases. Arch Dis Child. 2011;96(11):1042-1046.

The authors declare that there are no conflicts of interest present.