cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2024-4126HVJHBXcardiovascular-4126Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEW ARTICLESРоль желчных кислот в атерогенезе: обзорRole of bile acids in atherogenesis: reviewhttps://orcid.org/0000-0002-6104-8388СафарянА. С.SafaryanA. S.

Сафарян Ануш Сергеевна Сафарян — к.м.н., в.н.с. отдела профилактики метаболических нарушений.

Москва

Moscow

anush70@list.ruФГБУ "Национальный медицинский исследовательский центр терапии и профилактической медицины" Минздрава РоссииNational Medical Research Center for Therapy and Preventive Medicine202411092024231041264126Copyright © Сафарян А.С., 20242024Сафарян А.С.Safaryan A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/4126

В обзоре описывается метаболизм желчных кислот (ЖК) в организме человека, их влияние на обмен холестерина (ХС) и развитие атеросклероза, который остается одной из самых актуальных проблем в медицине. Обсуждается проблема холестаза, который часто встречается у пациентов с сердечно-сосудистыми заболеваниями, имеющими коморбидную патологию, в т.ч. и неалкогольную жировую болезнь печени и который играет ключевую роль в развитии множества осложнений, связанных с нарушением обмена ЖК, включая гиперлипидемию, метаболический синдром. Рассматриваются возможности лечения холестаза, позволяющего восстановить и нормальный уровень ХС. Показано, что при своевременном назначении урсодезоксихолевой кислоты можно предотвратить возникновение атеросклероза (первичная профилактика атеросклероза), т.к. при нормальном желчеобмене нормализуются уровни проатерогенных липидов и уменьшается продукция медиаторов воспаления, высокие уровни которых способствуют атерогенезу. В настоящем обзоре автор представляет важную роль желчеобмена в первичной и вторичной профилактике атеросклероза и возможность решения этого вопроса при помощи назначения урсодезоксихолевой кислоты и изменения образа жизни.

The review describes the metabolism of bile acids (BAs) in the human body, their effect on cholesterol metabolism and the development of atherosclerosis, which remains one of the most pressing problems in medicine. The problem of cholestasis is discussed, which is often found in patients with cardiovascular diseases with comorbidities, including non-alcoholic fatty liver disease and which plays a key role in the development of many complications associated with impaired BA metabolism, including hyperlipidemia, metabolic syndrome. Cholestasis treatment, which allows restoring normal cholesterol levels, are considered. Timely administration of ursodeoxycholic acid makes it possible to prevent atherosclerosis (primary prevention of atherosclerosis), because with normal bile metabolism, the levels of proatherogenic lipids are normalized and the production of inflammatory mediators, high levels of which contribute to atherogenesis, decreases. In this review, the author presents the important role of bile metabolism in the primary and secondary prevention of atherosclerosis and the possibility of solving this issue by prescribing ursodeoxycholic acid and changing lifestyle.

желчные кислотыхолестериндислипидемияатеросклерозпрофилактика атеросклерозамикробиота кишечникахолестазнеалкогольная жировая болезнь печениурсодезоксихолевая кислотаbile acidscholesteroldyslipidemiaatherosclerosisatherosclerosis preventiongut microbiotacholestasisnon-alcoholic fatty liver diseaseursodeoxycholic acidReferencesFan J, Watanabe T. Atherosclerosis: Known and unknown. Pathol Int. 2022;72(3):151-60. doi:10.1111/pin.13202.Fan J, Watanabe T. Atherosclerosis: Known and unknown. Pathol Int. 2022;72(3):151-60. doi:10.1111/pin.13202.Ежов М. В., Кухарчук В. В., Сергиенко И. В. и др. Нарушения липидного обмена. Клинические рекомендации 2023. Российский кардиологический журнал. 2023;28(5):5471. doi:10.15829/1560-4071-2023-5471.Ezhov MV, Kukharchuk VV, Sergienko IV, et al. Disorders of lipid me­tabolism. Clinical recommendations 2023. Russian Jour­nal of Cardiology. 2023;28(5):5471. (In Russ.) doi:10.15829/1560-4071-2023-5471.2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;290:140-205. doi:10.1016/j.atherosclerosis.2019.08.014.2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;290:140-205. doi:10.1016/j.atherosclerosis.2019.08.014.Pirillo A, Casula M, Catapano AL. European guidelines for the treatment of dyslipidaemias: New concepts and future challenges. Pharmacol Res. 2023:196:106936. doi:10.1016/j.phrs.2023.106936.Pirillo A, Casula M, Catapano AL. European guidelines for the treatment of dyslipidaemias: New concepts and future chal­lenges. Pharmacol Res. 2023:196:106936. doi:10.1016/j.phrs.2023.106936.Vodnala D, Rubenfire M, Brook RD. Secondary causes of dyslipidemia. Am J Cardiol. 2012;110(6):823-5. doi:10.1016/j.amjcard.2012.04.062.Vodnala D, Rubenfire M, Brook RD. Secondary causes of dyslipidemia. Am J Cardiol. 2012;110(6):823-5. doi:10.1016/j.amjcard.2012.04.062.Ершова А. И., Аль Раши Д. О., Иванова А. А. и др. Вторичные гиперлипидемии: этиология и патогенез. Российский кардиологический журнал. 2019;(5):74-81. doi:10.15829/1560-4071-2019-5-74-81.Ershova AI, Al Rashi DO, Ivanova AA, et al. Secondary hyper­lipidemia: etiology and pathogenesis. Russian Journal of Car­diology. 2019;(5):74-81. (In Russ.) doi:10.15829/1560-4071-2019-5-74-81.Ивашкин В. Т., Широкова Е. Н., Маевская М. В. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации и Российского общества по изучению печени по диагностике и лечению холестаза. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2015;25(2):41-57.Ivashkin VT, Shirokova YeN, Mayevskaya MV, et al. Clinical guidelines of the Russian gastroenterological association and the Russian society on study of the liver on diagnostics and treatment of cholestasis. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(2):41-57. (In Russ.)Alveirinho M, Freitas P, Faleiro ML. Role of gut microbiota in metabolic syndrome: a review of recent evidence. Porto Biomed J. 2020;5(6):e105. doi:10.1097/j.pbj.0000000000000105.Alveirinho M, Freitas P, Faleiro ML. Role of gut microbiota in me­tabolic syndrome: a review of recent evidence. Porto Biomed J. 2020;5(6):e105. doi:10.1097/j.pbj.0000000000000105.Воловникова В. А., Котрова А. Д., Иванова К. А. Роль кишечной микробиоты в развитии ожирения. Juvenis Scientia. 2019;6:4-10. doi:10.32415/jscientia.2019.06.01.Volovnikova VA, Kotrova AD, Ivanova KA, et al. Role of intestinal mi­crobiota in the development of obesity. Juvenis Scientia. 2019;6:4-10. (In Russ.) doi:10.32415/jscientia.2019.06.01.Евсютина Ю. В., Ивашкин В. Т. Метаболизм желчных кислот, заболевания печени и микробиом. Российский ж. гастроэнтерол гепатол колопроктол. 2018;28(2):4-10. doi:10.22416/1382-4376-2018-28-2-4-10.Yevsyutina YuV, Ivashkin VT. Metabolism of bile acids, liver di­seases and microbiome. Rus J Gastroenterol Hepatol Coloproctol. 2018;28(2):4-10. (In Russ.) doi:10.22416/1382-4376-2018-28-2-4-10.Porez G, Prawitt J, Gross B, et al. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res. 2012;53:1723-37. doi:10.1194/jlr.R024794.Porez G, Prawitt J, Gross B, et al. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res. 2012;53:1723-37. doi:10.1194/jlr.R024794.Arias IM, Alter HJ, Boyer JL, et al. Thorgeirsson, Allan W. Wolkoff. The Liver: Biology and Pathobiology. John Wiley & Sons, 2020. Total pages: 1152. ISBN: 1119436834, 9781119436836.Arias IM, Alter HJ, Boyer JL, et al. Thorgeirsson, Allan W. Wolkoff. The Liver: Biology and Pathobiology. John Wiley & Sons, 2020. Total pages: 1152. ISBN: 1119436834, 9781119436836.Hylemon PB, Zhou H, Pandak WM, et al. Bile acids as regulatory mo­lecules. J Lipid Res. 2009;50:1509-20. doi:10.1194/jlr.R900007-JLR200.Hylemon PB, Zhou H, Pandak WM, et al. Bile acids as regulatory mo­lecules. J Lipid Res. 2009;50:1509-20. doi:10.1194/jlr.R900007-JLR200.Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10:167-77. doi:10.1016/j.cmet.2009.08.001.Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10:167-77. doi:10.1016/j.cmet.2009.08.001.Guan B, Tong J, Hao H, et al. Bile acid coordinates micro­biota homeostasis and systemic immunometabolism in cardiometabolic diseases. Acta Pharm Sin B. 2022;12(5):2129-49. doi:10.1016/j.apsb.2021.12.011.Guan B, Tong J, Hao H, et al. Bile acid coordinates micro­biota homeostasis and systemic immunometabolism in cardiometabolic diseases. Acta Pharm Sin B. 2022;12(5):2129-49. doi:10.1016/j.apsb.2021.12.011.Hu YB, Liu XY, Zhan W. Farnesoid X receptor agonist INT-767 attenuates liver steatosis and inflammation in rat model of nonalcoholic steatohepatitis. Drug Des Devel Ther. 2018;12: 2213-21. doi:10.2147/DDDT.S170518.Hu YB, Liu XY, Zhan W. Farnesoid X receptor agonist INT-767 attenuates liver steatosis and inflammation in rat model of nonalcoholic steatohepatitis. Drug Des Devel Ther. 2018;12: 2213-21. doi:10.2147/DDDT.S170518.Yoo JY, Sniffen S, McGill Percy, et al. Gut Dysbiosis and Immu­ne System in Atherosclerotic Cardiovascular Disease (ACVD). Microorganisms. 2022;10:108. doi:10.3390/microorganisms10010108.Yoo JY, Sniffen S, McGill Percy, et al. Gut Dysbiosis and Immu­ne System in Atherosclerotic Cardiovascular Disease (ACVD). Micro­organisms. 2022;10:108. doi:10.3390/microorganisms10010108.Тюрюмин Я. Л., Шантуров В. А., Тюрюмина Е. Э. Физиология обмена холестерина (Обзор). Acta Biomedica Scientifica. 2012;2(1):153-8.Tyuryumin YaL, Shanturov VA, Tyuryumina EE. Physiology of cholesterol metabolism (The review). Acta Biomedica Scientifica. 2012;2(1):153-8. (In Russ.)Буторова Л. И. Холестероз желчного пузыря: патогенез, клиника, диагностика, принципы консервативной терапии: пособие для врачей. М.: Форте принт, 2012. 52 с. ISBN: 978-5-905757-04-4.Butorova LI. Cholesterosis of the gallbladder: pathogenesis, clinic, diagnosis, principles of conservative therapy: manual for doctors. Moscow: Forte Print, 2012. 52 p. (In Russ.) ISBN: 978-5-905757-04-4.Вахрушев Я. М., Горбунов А. Ю., Сучкова Е. В. и др. Желчнокаменная болезнь как возможное проявление системной патологии органов пищеварения. Терапервтический архив. 2015;87(2):54-8. doi:10.17116/terarkh201587254-58.Vakhrushev YaM, Gorbunov AYu, Tronina DV, et al. Cholelithiasis as a possible manifestation of systemic digestive diseases. Therapeutic Archive. 2015;87(2):54-8. (In Russ.) doi:10.17116/terarkh201587254-58.Полунина Т. Е. Холестаз: алгоритмы диагностики и лечения. Академия медицины и спорта. 2021;2(4):28-36. doi:10.15829/2712-7567-2021-43.Polunina TE. Cholestasis: algorithms for diagnosis and treat­ment. Academy of medicine and sports. 2021;2(4):28-36. (In Russ.) doi:10.15829/2712-7567-2021-43.Рекомендации экспертов Всероссийского научного общества кардиологов по диагностике и лечению метаболического синдрома. Второй пересмотр. под ред. И. Е. Чазовой. Практическая медицина. 2010;5(44):81-101.Recommendations of experts of the All-Russian Scientific Society of Cardiologists on the diagnosis and treatment of metabolic syn­drome. Second revision. ed. by I. Е. Chazova. Practical Medi­cine. 2010;5(44):81-101. (In Russ.)Baratta F, Pastori D, Angelico F et all. Nonalcoholic Fatty Liver Disease and Fibrosis Associated With Increased Risk of Cardiovascular Events in a Prospective Study. Clin Gastroenterol Hepatol. 2020;18(10):2324-31.e4. doi:10.1016/j.cgh.2019.12.026.Baratta F, Pastori D, Angelico F et all. Nonalcoholic Fatty Liver Disease and Fibrosis Associated With Increased Risk of Cardiovascular Events in a Prospective Study. Clin Gastroenterol Hepatol. 2020;18(10):2324-31.e4. doi:10.1016/j.cgh.2019.12.026.Галеева З.М, Гималетдинова И.А, Амиров Н. Б. Неалкогольная жировая болезнь печени и атерогенная дислипидемия. Какие проблемы возникают у кардиолога? Вестник современной клинической медицины. 2014;7(1):55-9.Galeeva ZM, Gimaletdinova IA, Amirov NB. Nonalcoholic fatty liver disease and atherogenic dyslipidemia. What problems arise in cardiologist? Bulletin of Modern Clinical Medicine. 2014;7(1):55-9. (In Russ.)Wu Sh, Wu F, Ding Y, et al. Association of non-alcoholic fatty liver di­sea­se with major adverse cardiovascular events: A systematic re­view and meta-analysis. Sci Rep. 2016;16:6:33386. doi:10.1038/srep33386.Wu Sh, Wu F, Ding Y, et al. Association of non-alcoholic fatty liver di­sea­se with major adverse cardiovascular events: A systematic re­view and meta-analysis. Sci Rep. 2016;16:6:33386. doi:10.1038/srep33386.Lepage P, Leclerc MC, Joossens M, et al. A metagenomic insight into our gut’s microbiome. Gut. 2013;62:146-58. doi:10.1136/gutjnl-2011-301805.Lepage P, Leclerc MC, Joossens M, et al. A metagenomic insight into our gut’s microbiome. Gut. 2013;62:146-58. doi:10.1136/gutjnl-2011-301805.Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65.Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65.Chen D, Yang Z, Chen X, et al. Effect of lactobacillus rhamnosus hsryfm 1301 on the gut microbiota and lipid metabolism in rats fed a high-fat diet. J Microbiol Biotechnol. 2015;25(5):687-95. doi:10.4014/jmb.1409.09085.Chen D, Yang Z, Chen X, et al. Effect of lactobacillus rhamnosus hsryfm 1301 on the gut microbiota and lipid metabolism in rats fed a high-fat diet. J Microbiol Biotechnol. 2015;25(5):687-95. doi:10.4014/jmb.1409.09085.Parasar B, Zhou H, Xiao X, et al. Chemoproteomic Profiling of Gut Microbiota-Associated Bile Salt Hydrolase Activity. 2019;5(5): 867-73. doi:10.1021/acscentsci.9b00147.Parasar B, Zhou H, Xiao X, et al. Chemoproteomic Profiling of Gut Microbiota-Associated Bile Salt Hydrolase Activity. 2019;5(5): 867-73. doi:10.1021/acscentsci.9b00147.Lye H-S, Kato T, Low W-Y, et al. Lactobacillus fermentum FTDC 8312 com­bats hypercholesterolemia via alteration of gut microbio­ta. Jour­nal of Biotechnology. 2017;262:75-83. doi:10.1016/j.jbiotec.2017.09.007.Lye H-S, Kato T, Low W-Y, et al. Lactobacillus fermentum FTDC 8312 com­bats hypercholesterolemia via alteration of gut microbio­ta. Jour­nal of Biotechnology. 2017;262:75-83. doi:10.1016/j.jbiotec.2017.09.007.Öner Ö, Aslim B, Aydaş SB. Mechanisms of cholesterol-lowering effects of lactobacilli and bifidobacteria strains as potential pro­biotics with their bsh gene analysis. 2014;24(1):12-8. doi:10.1159/000354316.Öner Ö, Aslim B, Aydaş SB. Mechanisms of cholesterol-lowering effects of lactobacilli and bifidobacteria strains as potential pro­biotics with their bsh gene analysis. 2014;24(1):12-8. doi:10.1159/000354316.Costabile A, Buttarazzi I, Kolida S, et al. An in vivo assessment of the cholesterollowering efficacy of lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. PLoS One. 2017;12(12):e0187964. doi:10.1371/journal.pone.0187964.Costabile A, Buttarazzi I, Kolida S, et al. An in vivo assessment of the cholesterollowering efficacy of lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. PLoS One. 2017;12(12):e0187964. doi:10.1371/journal.pone.0187964.Baars A, Oosting A, Lohuis M, et al. Sex differences in lipid metabolism are affected by presence of the gut microbiota. Sci Rep. 2018;8(1):13426. doi:10.1038/s41598-018-31695-w.Baars A, Oosting A, Lohuis M, et al. Sex differences in lipid metabolism are affected by presence of the gut microbiota. Sci Rep. 2018;8(1):13426. doi:10.1038/s41598-018-31695-w.Heinken A, Ravcheev DA, Baldini F, et al. Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease. Microbiome. 2019;7(1):75. doi:10.1186/s40168-019-0689-3.Heinken A, Ravcheev DA, Baldini F, et al. Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease. Microbiome. 2019;7(1):75. doi:10.1186/s40168-019-0689-3.Sayin SI, Wahlström A, Felin J, et al. Gutmicrobiota regulates bile acid metabolism by reducing the levels of taurobetamuricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013; 17(2):22535. doi:10.1016/j.cmet.2013.01.003.Sayin SI, Wahlström A, Felin J, et al. Gutmicrobiota regulates bile acid metabolism by reducing the levels of taurobetamuricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013; 17(2):22535. doi:10.1016/j.cmet.2013.01.003.Хавкин А. И., Волы­нец Г. В., Никитин А. В. Взаимосвязь кишечного микробиома и метаболизма желчных кислот. Вопросы практической педиатрии. 2020;15(1):53-60. doi:10.20953/1817-7646-2020-1-53-60.Khavkin AI, Volynets GV, Nikitin AV. Interrelation of intestinal mic­robiome and metabolism of bile acids. Voprosy prakticheskaya pediatriya. 2020;15(1):53-60. (In Russ.) doi:10.20953/1817-7646-2020-1-53-60.Gargari G, Deon V, Taverniti V, et al. Evidence of dysbiosis in the in­testinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake. FEMS. Microbiol Ecol. 2018;94:fiy045. doi:10.1093/femsec/fiy045.Gargari G, Deon V, Taverniti V, et al. Evidence of dysbiosis in the in­testinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake. FEMS. Microbiol Ecol. 2018;94:fiy045. doi:10.1093/femsec/fiy045.Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, et al. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Food Funct. 2016;7:1775-87. doi:10.1039/c5fo00886g.Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, et al. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Food Funct. 2016;7:1775-87. doi:10.1039/c5fo00886g.Koh A, De Vadder F, Kovatcheva-Datchary P, et al. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016;165:1332-45. doi:10.1016/j.cell.2016.05.041.Koh A, De Vadder F, Kovatcheva-Datchary P, et al. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016;165:1332-45. doi:10.1016/j.cell.2016.05.041.Dabke K, Hendrick G, Devkota S. The gut microbiome and meta­bolic syndrome. J Clin Investig. 2019;129:4050-7. doi:10.1172/JCI129194.Dabke K, Hendrick G, Devkota S. The gut microbiome and meta­bolic syndrome. J Clin Investig. 2019;129:4050-7. doi:10.1172/JCI129194.Kaska L, Sledzinski T, Chomiczewska A, et al. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol. 2016;22:8698-719. doi:10.3748/wjg.v22.i39.8698.Kaska L, Sledzinski T, Chomiczewska A, et al. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol. 2016;22:8698-719. doi:10.3748/wjg.v22.i39.8698.Cariou B, van Harmelen K, Duran-Sandoval D, et al. The farnesoid X re­ceptor modulates adiposity and peripheral insulin sensitivity in mi­ce. J Biol Chem. 2006;281:11039-49. doi:10.1074/jbc.M510258200.Cariou B, van Harmelen K, Duran-Sandoval D, et al. The farnesoid X re­ceptor modulates adiposity and peripheral insulin sensitivity in mi­ce. J Biol Chem. 2006;281:11039-49. doi:10.1074/jbc.M510258200.Langhi C, Le May C, Kourimate S, et al. Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes. FEBS. Lett. 2008;582:949-55. doi:10.1016/j.febslet.2008.02.038.Langhi C, Le May C, Kourimate S, et al. Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes. FEBS. Lett. 2008;582:949-55. doi:10.1016/j.febslet.2008.02.038.Барановский А. Ю., Райхельсон К. Л., Семенов Н. В. и др. Принципы лечения холестатических заболеваний печени. Лечащий врач. 2012;(07):43-50.Baranovsky AYu, Raikhelson KL, Semenov NV, et al. Principles of treatment of cholestatic liver diseases. The attending physician. 2012;(07):43-50. (In Russ.)Hilscher MB, Kamath PS, Eaton JE. Cholestatic Liver Diseases: A Primer for Generalists and Subspecialists. 2020 Mayo Foun­dation for Medical Education and Research. Mayo Clin Proc. 2020;95(10):2263-79. doi:10.1016/j.mayocp.2020.01.015.Hilscher MB, Kamath PS, Eaton JE. Cholestatic Liver Diseases: A Primer for Generalists and Subspecialists. 2020 Mayo Foun­dation for Medical Education and Research. Mayo Clin Proc. 2020;95(10):2263-79. doi:10.1016/j.mayocp.2020.01.015.Драпкина О. М., Буеверова Е. Л. Урсодезоксихолевая кислота: терапевтическая ниша в практике интерниста. Терапевтический архив. 2015;87(4):84-90. doi:10.17116/terarkh201587484-90.Drapkina OM, Bueverova EL. Ursodeoxycholic acid: therapeutic niche in the internist's practice. Therapeutic Archive. 2015; 87(4):84-90. (In Russ.) doi:10.17116/terarkh201587484-90.Guarino MPL, Cocca S, Altomare A, et al. Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed. World J Gastroenterol. 2013;19(31):5029-34. doi:10.3748/wjg.v19.i31.5029.Guarino MPL, Cocca S, Altomare A, et al. Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed. World J Gastroenterol. 2013;19(31):5029-34. doi:10.3748/wjg.v19.i31.5029.Bode N, Grebe A, Kerksiek Ф, et al. Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice. Biochem Biophys Res Commun. 2016;478(1):356-62. doi:10.1016/j.bbrc.2016.07.047.Bode N, Grebe A, Kerksiek Ф, et al. Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice. Biochem Biophys Res Commun. 2016;478(1):356-62. doi:10.1016/j.bbrc.2016.07.047.Nadinskaia М, Maevskaya М, Ivashkin V, et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959-75. doi:10.3748/wjg.v27.i10.959.Nadinskaia М, Maevskaya М, Ivashkin V, et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959-75. doi:10.3748/wjg.v27.i10.959.Huang K, Liu C, Peng M, et al. Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E-Deficient Mice. J Am Heart Assoc. 2021;10(7): e019820. doi:10.1161/JAHA.120.019820.Huang K, Liu C, Peng M, et al. Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E-Deficient Mice. J Am Heart Assoc. 2021;10(7): e019820. doi:10.1161/JAHA.120.019820.Simental-Mendía LE, Simental-Mendía M, Sánchez-García A, et al. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of rando­mized placebo-controlled trials. Lipids Health Dis. 2019;18(1):88. doi:10.1186/s12944-019-1041-4.Simental-Mendía LE, Simental-Mendía M, Sánchez-García A, et al. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis. 2019;18(1):88. doi:10.1186/s12944-019-1041-4.Cabezas Gelabert R. Efecto del acido ursodesoxicolico combinado con estatinas para el tratamiento de la hipercolesterolemia: ensayo clinico prospectivo. Rev Clin Esp. 2004; 204(12):632-5. doi:10.1016/s0014-2565(04)71566-0.Cabezas Gelabert R. Efecto del acido ursodesoxicolico combinado con estatinas para el tratamiento de la hipercolesterolemia: ensayo clinico prospectivo. Rev Clin Esp. 2004; 204(12):632-5. doi:10.1016/s0014-2565(04)71566-0.Марцевич С. Ю., Кутишенко Н. П., Дроздова Л. Ю. и др. Изучение влияния урсодезоксихолиевой кислоты на эффективность и безопасность терапии статинами у больных с заболеваниями печени, желчного пузыря и/или желчевыводящих путей (исследование РАКУРС). Рациональная Фармакотерапия в Кардиологии. 2014;10(2):147-52. doi:10.20996/1819-6446-2014-10-2-147-152.Martsevich SYu, Kutishenko NP, Drozdova Lyu, et al. Study of the effect of ursodeoxycholic acid on the efficacy and safety of statin therapy in patients with liver, gallbladder and/or biliary tract diseases (RACURS study). Rational Pharmacotherapy in Cardiology. 2014;10(2):147-52. (In Russ.) doi:10.20996/1819-6446-2014-10-2-147-152.

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