surgumedВестник СурГУ. МедицинаVestnik SurGU. Meditsina2949-3447Сургутский государственный университет10.34822/2304-9448-2022-1-67-72surgumed-516Research ArticleМЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИ. ОБЗОР ЛИТЕРАТУРЫLIFE SCIENCES. REVIEWSРОЛЬ ТРИМЕТИЛАМИНА N-ОКСИДА В РАЗВИТИИ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ: ВОЗМОЖНЫЕ СТРАТЕГИИ ТЕРАПИИ И ПРОФИЛАКТИКИTHE ROLE OF TRIMETHYLAMINE N-OXIDE IN HEART FAILURE DEVELOPMENT: POSSIBLE THERAPY AND PREVENTION STRATEGIEShttps://orcid.org/0000-0002-9356-2349КавушевскаяН. С.KavushevskayaN. S.

кандидат биологических наукE-mail: kavushevskaya_ns@surgu.ru

Candidate of Sciences (Biology)E-mail: kavushevskaya_ns@surgu.ru

https://orcid.org/0000-0001-6079-8841СинюковаТ. А.SinyukovaT. A.

кандидат биологических наукE-mail: proles@bk.ru

LecturerE-mail: proles@bk.ru

https://orcid.org/0000-0002-0918-7129КоваленкоЛ. В.KovalenkoL. V.

доктор медицинских наук, профессорE-mail: kovalenko_lv@surgu.ru

Doctor of Sciences (Medicine), ProfessorE-mail: kovalenko_lv@surgu.ru

https://orcid.org/0000-0001-9937-9767Тер-АветикянЛ. Г.Ter-AvetikyanL. G.

аспирант

Postgraduate

ШестаковаВ. А.ShestakovaV. A.

студент

Student

Сургутский государственный университет, СургутРоссияSurgut State University, SurgutRussian Federation20220906202201 (51)6772Copyright © Кавушевская Н.С., Синюкова Т.А., Коваленко Л.В., Тер-Аветикян Л.Г., Шестакова В.А., 20222022Кавушевская Н.С., Синюкова Т.А., Коваленко Л.В., Тер-Аветикян Л.Г., Шестакова В.А.Kavushevskaya N.S., Sinyukova T.A., Kovalenko L.V., Ter-Avetikyan L.G., Shestakova V.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.surgumed.ru/jour/article/view/516

Цель – анализ и систематизация актуальных сведений из научных изданий о роли триметиламина N-оксида в развитии сердечной недостаточности, а также прогнозирование возможности коррекции кишечного микробиома с помощью растительных полифенолов в контексте концепции взаимодействия «кишечник – сердце». Материалы и методы. Информационный поиск проведен по ключевым словам, объединенным в блоки для выявления различных аспектов изучаемой темы. Проанализированы научные публикации в отечественных и зарубежных базах данных eLIBRARY.RU, Web of Science, Scopus, Springer. Глубина поиска – 10 лет. Результаты. Показана высокая прогностическая значимость уровня триметиламина N-оксида в развитии сердечной недостаточности, что позволяет рассматривать растительные полифенолы как перспективные биологически активные соединения, терапевтический потенциал влияния которых на сердечную недостаточность требует дальнейших экспериментальных исследований.

The study aims to analyze and systemize current information obtained from the scientific literature on the role of trimethylamine N-oxide in the development of heart failure, and to predict the possibilities of gut microbiome correction using plant polyphenols in the concept of “bowel – heart” relation. Materials and methods. The information search was carried out using keywords combined into groups to detect various aspects of the topic under study. The scientific literature for the past 10 years was analyzed from such Russian and foreign databases as eLIBRARY.RU, Web of Science, Scopus, Springer. Results. Consideration of plant polyphenols as highpotential biological active compounds is possible due to the high predictive value of trimethylamine N-oxide level in the development of heart failure. The therapeutic potential of these compounds affecting the heart failure requires further experimental research.

сердечная недостаточностьмикробиоммикробиота кишечникаполифенолыполифенолы растений семейства ВересковыеТМАОтриметиламина N-оксидтриметиламиндоксидheart failuremicrobiomegut microbiotapolyphenolsvacciniaceous plants polyphenolsTMAOtrimethylamine N-oxidetrimethylamine oxideReferencesZiaeian B., Fonarow G. C. Epidemiology and Aetiology of Heart Failure // Nat Rev Cardiol. 2016. Vol. 13, Is. 6. P. 368–378. DOI 10.1038/nrcardio.2016.25.Ziaeian B., Fonarow G. C. Epidemiology and Aetiology of Heart Failure // Nat Rev Cardiol. 2016. Vol. 13, Is. 6. P. 368–378. DOI 10.1038/nrcardio.2016.25.Andersson C., Hansen P. W., Steffensen I. E. et al. Mortality Associated with Cardiovascular Drugs in Patients with Chronic Obstructive Pulmonary Disease and Right-Sided Heart Failure – A Danish Nationwide Registry-Based Study // Eur J Intern Med. 2019. Vol. 63. P. 56–61. DOI 10.1016/j.ejim.2019.02.014.Andersson C., Hansen P. W., Steffensen I. E. et al. Mortality Associated with Cardiovascular Drugs in Patients with Chronic Obstructive Pulmonary Disease and Right-Sided Heart Failure – A Danish Nationwide Registry-Based Study // Eur J Intern Med. 2019. Vol. 63. P. 56–61. DOI 10.1016/j.ejim.2019.02.014.Tomasoni D., Adamo M., Lombardi C. M., Metra M. Highlights in Heart Failure // ESC Heart Fail. 2019. Vol. 6, Is. 6. P. 1105–1127. DOI 10.1002/ehf2.12555.Tomasoni D., Adamo M., Lombardi C. M., Metra M. Highlights in Heart Failure // ESC Heart Fail. 2019. Vol. 6, Is. 6. P. 1105–1127. DOI 10.1002/ehf2.12555.Salzano A., Cassambai S., Yazaki Y. et al. The Gut Axis Involvement in Heart Failure Focus on Trimethylamine N-Oxide // Heart Fail Clin. 2020. Vol. 16, Is. 1. P. 23–31. DOI 10.1016/j.hfc.2019.08.001.Salzano A., Cassambai S., Yazaki Y. et al. The Gut Axis Involvement in Heart Failure Focus on Trimethylamine N-Oxide // Heart Fail Clin. 2020. Vol. 16, Is. 1. P. 23–31. DOI 10.1016/j.hfc.2019.08.001.Gessner A., di Giuseppe R., Koch K., Fromm M. F., Lieb W., Maas R. Trimethylamine-N-Oxide (TMAO) Determined by LC-MS/MS: Distribution and Correlates in the Population-Based Popgen Cohort // Clin Chem Lab Med. 2020. Vol. 58, No. 5. P. 733–740.Gessner A., di Giuseppe R., Koch K., Fromm M. F., Lieb W., Maas R. Trimethylamine-N-Oxide (TMAO) Determined by LC-MS/MS: Distribution and Correlates in the Population-Based Popgen Cohort // Clin Chem Lab Med. 2020. Vol. 58, No. 5. P. 733–740.Subramaniam S., Fletcher C. Trimethylamine N-Oxide: Breathe New Life // Br J Pharmacol. 2018. Vol. 175, Is. 8. P. 1344–1353.Subramaniam S., Fletcher C. Trimethylamine N-Oxide: Breathe New Life // Br J Pharmacol. 2018. Vol. 175, Is. 8. P. 1344–1353.Gibson R., Lau C.-H. E., Loo R. L. et al. The Association of Fish Consumption and Its Urinary Metabolites with Cardiovascular Risk Factors: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) // Am J Clin Nutr. 2019. Vol. 11, Is. 2. P. 280–290.Gibson R., Lau C.-H. E., Loo R. L. et al. The Association of Fish Consumption and Its Urinary Metabolites with Cardiovascular Risk Factors: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) // Am J Clin Nutr. 2019. Vol. 11, Is. 2. P. 280–290.Al-Rubaye H., Perfetti G., Kaski J.-C. The Role of Microbiota in Cardiovascular Risk: Focus on Trimethylamine Oxide // Curr Probl Cardiol. 2019. Vol. 44, Is. 6. P. 182–196.Al-Rubaye H., Perfetti G., Kaski J.-C. The Role of Microbiota in Cardiovascular Risk: Focus on Trimethylamine Oxide // Curr Probl Cardiol. 2019. Vol. 44, Is. 6. P. 182–196.Janeiro M. H., Ramírez M. J., Milagro F. I., Martínez J. A., Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target // Nutrients. 2018. Vol. 10, Is. 10. P. 1398.Janeiro M. H., Ramírez M. J., Milagro F. I., Martínez J. A., Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target // Nutrients. 2018. Vol. 10, Is. 10. P. 1398.Fennema D., Phillips I. R., Shephard E. A. Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease // Drug Metab Dispos. 2016. Vol. 44, Is. 11. P. 1839–1850.Fennema D., Phillips I. R., Shephard E. A. Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease // Drug Metab Dispos. 2016. Vol. 44, Is. 11. P. 1839–1850.Cho C. E., Taesuwan S., Malysheva O. V. et al. Trimethylamine-NOxide (TMAO) Response to Animal Source Foods Varies among Healthy Young Men and Is Influenced by Their Gut Microbiota Composition: A Randomized Controlled Trial // Mol Nutr Food Res. 2017. Vol. 61, Is. 1. P. 256–259.Cho C. E., Taesuwan S., Malysheva O. V. et al. Trimethylamine-NOxide (TMAO) Response to Animal Source Foods Varies among Healthy Young Men and Is Influenced by Their Gut Microbiota Composition: A Randomized Controlled Trial // Mol Nutr Food Res. 2017. Vol. 61, Is. 1. P. 256–259.Velasquez M. T., Ramezani A., Manal A., Raj D. S. Trimethylamine N-Oxide: The Good, the Bad and the Unknown // Toxins (Basel). 2016. Vol. 8, Is. 11. P. 326.Velasquez M. T., Ramezani A., Manal A., Raj D. S. Trimethylamine N-Oxide: The Good, the Bad and the Unknown // Toxins (Basel). 2016. Vol. 8, Is. 11. P. 326.Papandreou C., Moré M., Bellamine A. Trimethylamine N-Oxide in Relation to Cardiometabolic Health-Cause or Effect? // Nutrients. 2020. Vol. 12, Is. 5. P. 1330.Papandreou C., Moré M., Bellamine A. Trimethylamine N-Oxide in Relation to Cardiometabolic Health-Cause or Effect? // Nutrients. 2020. Vol. 12, Is. 5. P. 1330.Chhibber-Goel J., Gaur A., Singhal V., Parakh N., Bhargava B., Sharma A. The Complex Metabolism of Trimethylamine in Humans: Endogenous and Exogenous Sources // Expert Rev Mol Med. 2016. Vol. 18. P. e8. DOI 10.1017/erm.2016.6.Chhibber-Goel J., Gaur A., Singhal V., Parakh N., Bhargava B., Sharma A. The Complex Metabolism of Trimethylamine in Humans: Endogenous and Exogenous Sources // Expert Rev Mol Med. 2016. Vol. 18. P. e8. DOI 10.1017/erm.2016.6.Van Hecke T., Jakobsen L. M., Vossen E. et al. Short-Term Beef Consumption Promotes Systemic Oxidative Stress, TMAO Formation and Inflammation in Rats, and Dietary Fat Content Modulates These Effects // Food Funct. 2016. Vol. 7, Is. 9. P. 3760–3771.Van Hecke T., Jakobsen L. M., Vossen E. et al. Short-Term Beef Consumption Promotes Systemic Oxidative Stress, TMAO Formation and Inflammation in Rats, and Dietary Fat Content Modulates These Effects // Food Funct. 2016. Vol. 7, Is. 9. P. 3760–3771.Koeth R. A., Wang Z., Levison B. S. et al. Intestinal Microbiota Metabolism of L-Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis // Nat Med. 2013. Vol. 19, Is. 5. P. 576–585. DOI 10.1038/nm.3145.Koeth R. A., Wang Z., Levison B. S. et al. Intestinal Microbiota Metabolism of L-Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis // Nat Med. 2013. Vol. 19, Is. 5. P. 576–585. DOI 10.1038/nm.3145.Pignanelli M., Bogiatzi C., Gloor G. et al. Moderate Renal Impairment and Toxic Metabolites Produced by the Intestinal Microbiome: Dietary Implications // J Ren Nutr. 2019. Vol. 29. P. 55–64.Pignanelli M., Bogiatzi C., Gloor G. et al. Moderate Renal Impairment and Toxic Metabolites Produced by the Intestinal Microbiome: Dietary Implications // J Ren Nutr. 2019. Vol. 29. P. 55–64.Rohrmann S., Linseisen J., Allenspach M., von Eckardstein A., Müller D. Plasma Concentrations of Trimethylamine-N-Oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population // J Nutr. 2016. Vol. 146, Is. 2. P. 283–289.Rohrmann S., Linseisen J., Allenspach M., von Eckardstein A., Müller D. Plasma Concentrations of Trimethylamine-N-Oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population // J Nutr. 2016. Vol. 146, Is. 2. P. 283–289.Zhu Ch., Sawrey-Kubicek L., Bardagjy A. S. et al. Whole EggZhu Ch., Sawrey-Kubicek L., Bardagjy A. S. et al. Whole EggConsumption Increases Plasma Choline and Betaine without Affecting TMAO Levels or Gut Microbiome in Overweight Postmenopausal Women // Nutr Res. 2020. Vol. 78. P. 36–41.Consumption Increases Plasma Choline and Betaine without Affecting TMAO Levels or Gut Microbiome in Overweight Postmenopausal Women // Nutr Res. 2020. Vol. 78. P. 36–41.Tang W. H., Wang Z., Fan Y. et al. Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-NOxide in Patients with Heart Failure: Refining the Gut Hypothesis // J Am Coll Cardiol. 2014. Vol. 64, Is. 18. P. 1908–1914. DOI 10.1016/j.jacc.2014.02.617.Tang W. H., Wang Z., Fan Y. et al. Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-NOxide in Patients with Heart Failure: Refining the Gut Hypothesis // J Am Coll Cardiol. 2014. Vol. 64, Is. 18. P. 1908–1914. DOI 10.1016/j.jacc.2014.02.617.Burton K. J., Krüger R., Scherz V. et al. Trimethylamine-N-Oxide Postprandial Response in Plasma and Urine Is Lower after Fermented Compared to Non-Fermented Dairy Consumption in Healthy Adults // Nutrients. 2020. Vol. 12, Is. 1. P. 234.Burton K. J., Krüger R., Scherz V. et al. Trimethylamine-N-Oxide Postprandial Response in Plasma and Urine Is Lower after Fermented Compared to Non-Fermented Dairy Consumption in Healthy Adults // Nutrients. 2020. Vol. 12, Is. 1. P. 234.Schmedes M., Balderas C., Aadland E. K. et al. The Effect of Lean-Seafood and Non-Seafood Diets on Fasting and Postprandial Serum Metabolites and Lipid Species: Results from a Randomized Crossover Intervention Study in Healthy Adults // Nutrients. 2018. Vol. 10, Is. 5. P. 598. 23. Hamaya R., Ivey K. L., Lee D. H. et al. Association of Diet with Circulating Trimethylamine-N-Oxide Concentration // Am J Clin Nutr. 2020. Vol. 112, Is. 6. P. 1448–1455.Schmedes M., Balderas C., Aadland E. K. et al. The Effect of Lean-Seafood and Non-Seafood Diets on Fasting and Postprandial Serum Metabolites and Lipid Species: Results from a Randomized Crossover Intervention Study in Healthy Adults // Nutrients. 2018. Vol. 10, Is. 5. P. 598. 23. Hamaya R., Ivey K. L., Lee D. H. et al. Association of Diet with Circulating Trimethylamine-N-Oxide Concentration // Am J Clin Nutr. 2020. Vol. 112, Is. 6. P. 1448–1455.Mutharasan R. K., Kansal P., Jackson H. A. et al. Heart Failure Care Transitions: Queuing Theory-Based Cost-Effectiveness Analysis of Outpatient Clinic Capacity Sizing // J Am Coll Cardiol. 2017. Vol. 69, Is. 11. P. 2508. DOI 10.1016/S0735-1097(17)35897-7.Mutharasan R. K., Kansal P., Jackson H. A. et al. Heart Failure Care Transitions: Queuing Theory-Based Cost-Effectiveness Analysis of Outpatient Clinic Capacity Sizing // J Am Coll Cardiol. 2017. Vol. 69, Is. 11. P. 2508. DOI 10.1016/S0735-1097(17)35897-7.Шляхто Е. В., Звартау Н. Э., Виллевальде С. В. и др. Реализованные модели и элементы организации медицинской помощи пациентам с сердечной недостаточностью в регионах Российской Федерации: перспективы трансформации в региональные системы управления сердечно-сосудистыми рисками // Рос. кардиолог. журн. 2020. Т. 25, № 4. С. 9–18. DOI 10.15829/1560-4071-2020-4-3792.Шляхто Е. В., Звартау Н. Э., Виллевальде С. В. и др. Реализованные модели и элементы организации медицинской помощи пациентам с сердечной недостаточностью в регионах Российской Федерации: перспективы трансформации в региональные системы управления сердечно-сосудистыми рисками // Рос. кардиолог. журн. 2020. Т. 25, № 4. С. 9–18. DOI 10.15829/1560-4071-2020-4-3792.Krack A., Sharma R., Figulla H. R., Anker S. D. The Importance of the Gastrointestinal System in the Pathogenesis of Heart Failure // European Heart Journal. 2005. Vol. 26, Is. 22. P. 2368–2374. DOI 10.1093/eurheartj/ehi389.Krack A., Sharma R., Figulla H. R., Anker S. D. The Importance of the Gastrointestinal System in the Pathogenesis of Heart Failure // European Heart Journal. 2005. Vol. 26, Is. 22. P. 2368–2374. DOI 10.1093/eurheartj/ehi389.Zhou X., Jin M. C., Liu L. et al. Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with Chronic Heart Failure after Myocardial Infarction // ESC Heart Failure. 2020. Vol. 7, Is. 1. P. 189–194. DOI 10.1002/ehf2.12552.Zhou X., Jin M. C., Liu L. et al. Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with Chronic Heart Failure after Myocardial Infarction // ESC Heart Failure. 2020. Vol. 7, Is. 1. P. 189–194. DOI 10.1002/ehf2.12552.Драпкина О. М., Кабурова А. Н. Состав и метаболиты кишечной микробиоты как новые детерминанты развития сердечно-сосудистой патологии // Рациональная фармакотерапия в кардиологии. 2020 Т. 16, № 2. С. 277–285. DOI 10.20996/1819-6446-2020-04-02.Драпкина О. М., Кабурова А. Н. Состав и метаболиты кишечной микробиоты как новые детерминанты развития сердечно-сосудистой патологии // Рациональная фармакотерапия в кардиологии. 2020 Т. 16, № 2. С. 277–285. DOI 10.20996/1819-6446-2020-04-02.Tang W. H., Wang Z., Fan Y. et al. Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-NOxide in Patients with Heart Failure: Refining the Gut Hypothesis // J Am Coll Cardiol. 2014. Vol. 64, Is. 18. P. 1908–1914. DOI 10.1016/j. jacc.2014.02.617.Tang W. H., Wang Z., Fan Y. et al. Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-NOxide in Patients with Heart Failure: Refining the Gut Hypothesis // J Am Coll Cardiol. 2014. Vol. 64, Is. 18. P. 1908–1914. DOI 10.1016/j. jacc.2014.02.617.Healey G. R., Murphy R., Brough L. et al. Interindividual Variability in Gut Microbiota and Host Response to Dietary Interventions // Nutr Rev. 2017. Vol. 75, Is. 12. P. 1059–1080. DOI 10.1093/nutrit/nux062.Healey G. R., Murphy R., Brough L. et al. Interindividual Variability in Gut Microbiota and Host Response to Dietary Interventions // Nutr Rev. 2017. Vol. 75, Is. 12. P. 1059–1080. DOI 10.1093/nutrit/nux062.Duda-Chodak A. The Inhibitory Effect of Polyphenols on Human Gut // J Physiol Pharmacol. 2012. Vol. 63, Is. 5. P. 497–503.Duda-Chodak A. The Inhibitory Effect of Polyphenols on Human Gut // J Physiol Pharmacol. 2012. Vol. 63, Is. 5. P. 497–503.Kawabata K., Yoshioka Y., Terao J. Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols // Molecules. 2019. Vol. 24, Is. 2. DOI 10.3390/molecules24020370.Kawabata K., Yoshioka Y., Terao J. Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols // Molecules. 2019. Vol. 24, Is. 2. DOI 10.3390/molecules24020370.Sreng N., Champion S., Martin J. C. et al. Resveratrol-Mediated Glycemic Regulation Is Blunted by Curcumin and Is Associated to Modulation of Gut Microbiota // J Nutr Biochem. 2019. Vol. 72. P. 108218. DOI 10.1016/j.jnutbio.2019.108218.Sreng N., Champion S., Martin J. C. et al. Resveratrol-Mediated Glycemic Regulation Is Blunted by Curcumin and Is Associated to Modulation of Gut Microbiota // J Nutr Biochem. 2019. Vol. 72. P. 108218. DOI 10.1016/j.jnutbio.2019.108218.Wood E., Hein S., Heiss C. et al. Blueberries and Cardiovascular Disease Prevention // Food Funct. 2019. Vol. 10, Is. 12. P. 7621–7633. DOI 10.1039/c9fo02291k.Wood E., Hein S., Heiss C. et al. Blueberries and Cardiovascular Disease Prevention // Food Funct. 2019. Vol. 10, Is. 12. P. 7621–7633. DOI 10.1039/c9fo02291k.

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