Триметиламин- N-оксид (ТМАО) в патогенезе ревматоидного артрита и сердечно- сосудистых осложнений
https://doi.org/10.31146/1682-8658-ecg-244-12-127-134
Аннотация
Ревматоидный артрит представляет собой многокомпонентное аутоиммунное расстройство, основными проявлениями которого служат хроническое воспаление и деструкция суставных тканей. В последние годы ключевую роль в его патогенезе отводят кишечному микробиому и его метаболитам, среди которых триметиламин-N-оксид (ТМАО) привлекает особое внимание. Кишечная микробиота- экосистема, включающая множество микроорганизмов и продукты их метаболизма, - выполняет ключевую функцию в регуляции иммунного баланса. Нарушение ее состава (дисбиоз) ассоциировано с широким спектром аутоиммунных патологий, в том числе ревматоидным артритом.
Ключевые слова
Об авторах
Л. В. Тарасова
Федеральное государственное бюджетное образовательное учреждение высшего образования «Чувашский государственный университет имени И.Н. Ульянова»
Россия
Россия
К. А. Кокурина
Федеральное государственное бюджетное образовательное учреждение высшего образования «Чувашский государственный университет имени И.Н. Ульянова»
Россия
Россия
Ю. В. Цыганова
Федеральное государственное бюджетное образовательное учреждение высшего образования «Чувашский государственный университет имени И.Н. Ульянова»
Россия
Россия
Список литературы
1. Li D., Ke Y., Zhan R. et al. Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell. 2018;17 (4): e12768. doi: 10.1111/acel.12768.
2. Hoyles L., Jiménez-Pranteda M.L., Chilloux J. et al. Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota. Microbiome. 2018;6 (1):73. doi: 10.1186/s40168-018-0461-0.
3. 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: e02481-14.
4. Hisamuddin I.M., Yang V.W. Genetic polymorphisms of human flavin-containing monooxygenase 3: Implications for drug metabolism and clinical perspectives. Pharmacogenomics. 2007;(8):635-643. doi: 10.2217/14622416.8.6.635.
5. Al-Waiz M., Mitchell S., Idle J., Smith, R. The metabolism of 14C-labelled trimethylamine and its N-oxide in man. Xenobiotica. 1987;17 (5):551-558. doi: 10.3109/00498258709043962.
6. Ufnal M., Zadlo A., Ostaszewski R. Tmao: A small molecule of great expectations. Nutrition. 2015;31 (11-12), 1317-1323. doi: 10.1016/j.nut.2015.05.006.
7. Ganguly P., Boserman P., van der Vegt N.F.A., Shea J.E. Trimethylamine N-Oxide Counteracts Urea Denaturation by Inhibiting Protein-Urea Preferential Interaction. J. Am. Chem. Soc. 2018;140:483-492.
8. Jethva P.N., Udgaonkar J.B. The Osmolyte TMAO Modulates Protein Folding Cooperativity by Altering Global Protein Stability. Biochemistry. 2018;57:5851-5863.
9. Bennett B.J., de Aguiar Vallim T.Q., et al. Trimethylamine-N-Oxide, a Metabolite Associated with Atherosclerosis, Exhibits Complex Genetic and Dietary Regulation. Cell Metab. 2013;17:49-60.
10. Kerley C.P. Dietary Patterns and Components to Prevent and Treat Heart Failure: A Comprehensive Review of Human Studies. Nutr. Res. Rev. 2019;32:1-27.
11. Belkaid Y., Hand T.W. Role of the microbiota in immunity and inflammation. Cell. 2014;157 (1):121-141. doi: 10.1016/j.cell.2014.03.011.
12. Hansson G.K. Atherosclerosis-an immune disease: the Anitschkov Lecture 2007. Atherosclerosis. 2009;202 (1):2-10. doi: 10.1016/j.atherosclerosis.2008.08.039.
13. Rodriguez-Iturbe B., Johnson R.J. Heat shock proteins and cardiovascular disease. Physiol.Int. 2018;105 (1):19-37. doi: 10.1556/2060.105.2018.1.4.
14. Wick G., Knoflach M., Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu. Rev. Immunol. 2004;22:361-403. doi: 10.1146/annurev.immunol.22.012703.104644.
15. Wick G., Jakic B., Buszko M., Wick M.C., Grundtman C. The role of heat shock proteins in atherosclerosis. Nat. Rev. Cardiol. 2014;11 (9):516-529. doi: 10.1038/nrcardio.2014.91.
16. Khandia R., Munjal A.K., Iqbal H.M.N., Dhama K. Heat Shock Proteins: Therapeutic Perspectives in Inflammatory Disorders. Recent Pat. Inflammation Allergy Drug Discovery. 2017;10 (2):94-104. doi: 10.2174/1872213x10666161213163301.
17. Mohammadi A., Vahabzadeh Z., Jamalzadeh S., Khalili T. Trimethylamine-N-oxide, as a risk factor for atherosclerosis, induces stress in J774A.1 murine macrophages. Adv. Med. Sci. 2018;63 (1):57-63. doi: 10.1016/j.advms.2017.06.006.
18. Mohammadi A., Gholamhoseyniannajar A., Yaghoobi M.M., Jahani Y., Vahabzadeh Z. Expression levels of heat shock protein 60 and glucose-regulated protein 78 in response to trimethylamine-N-oxide treatment in murine macrophage J774A.1 cell line. Cell Mol. Biol. (Noisy-le-grand). 2015;61 (4), 94-100.
19. Schroder K., Tschopp J. The inflammasomes. Cell. 2010;140 (6):821-832. doi: 10.1016/j.cell.2010.01.040.
20. Maiolino G., Rossitto G., Caielli P., Bisogni V., Rossi G.P., Calo L.A. The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts. Mediators Inflammation. 2013:714653. doi: 10.1155/2013/714653.
21. Jin P., Bian Y., Wang K., Cong G., Yan R., Sha Y. Homocysteine accelerates atherosclerosis via inhibiting LXRalpha-mediated ABCA1/ABCG1-dependent cholesterol efflux from macrophages. Life Sci. 2018;214:41-50. doi: 10.1016/j.lfs.2018.10.060.
22. Wang Z., Klipfell E., Bennett B.J., Koeth R., Levison B.S., Dugar B. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472 (7341):57-63. doi: 10.1038/nature09922.
23. Geng J., Yang C., Wang B., Zhang X., Hu T., Gu Y. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. BioMed. Pharmacother. 2018;97:941-947. doi: 10.1016/j.biopha.2017.11.016.
24. Hoseini Z., Sepahvand F., Rashidi B., Sahebkar A., Masoudifar A., Mirzaei H. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis. J. Cell Physiol. 2018;233 (3):2116-2132. doi: 10.1002/jcp.25930.
25. Takahashi M. NLRP3 inflammasome as a novel player in myocardial infarction.Int. Heart J. 2014;55 (2):101-105. doi: 10.1536/ihj.13-388,
26. Boini K.M., Hussain T., Li P.L., Koka S. Trimethylamine-N-Oxide Instigates NLRP3 Inflammasome Activation and Endothelial Dysfunction. Cell Physiol. Biochem. 2017;44 (1):152-162. doi: 10.1159/000484623.
27. Wang R., Wang Y., Mu N., Lou X., Li W., Chen Y. Activation of NLRP3 inflammasomes contributes to hyperhomocysteinemia-aggravated inflammation and atherosclerosis in apoE-deficient mice. Lab. Invest. 2017;97 (8):922. doi: 10.1038/labinvest.2017.30.
28. Chen M.L., Zhu X.H., Ran L., Lang H.D., Yi L., Mi M.T. Trimethylamine-N-Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3-SOD2-mtROS Signaling Pathway. J. Am. Heart Assoc. 2017;6 (9): e006347. doi: 10.1161/jaha.117.006347.
29. Sho T., Xu J. Role and mechanism of ROS scavengers in alleviating NLRP3-mediated inflammation. Biotechnol. Appl. Biochem. 2019;66 (1):4-13. doi: 10.1002/bab.1700.
30. Yue C., Yang X., Li J., Chen X., Zhao X., Chen Y. Trimethylamine N-oxide prime NLRP3 inflammasome via inhibiting ATG16L1-induced autophagy in colonic epithelial cells. Biochem. Biophys. Res.Commun. 2017;490 (2):541-551. doi: 10.1016/j.bbrc.2017.06.075.
31. Sun X., Jiao X., Ma Y., Liu Y., Zhang L., He Y. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem. Biophys. Res.Commun. 2016;481 (1-2):63-70. doi: 10.1016/j.bbrc.2016.11.017.
32. Yue C., Yang X., Li J., Chen X., Zhao X., Chen Y. Trimethylamine N-oxide prime NLRP3 inflammasome via inhibiting ATG16L1-induced autophagy in colonic epithelial cells. Biochem. Biophys. Res.Commun. 2017;490 (2):541-551. doi: 10.1016/j.bbrc.2017.06.075.
33. Janeiro M.H., Ramirez M.J., Milagro F.I., Martinez J.A., Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients. 2018;10 (10);1398-1419. doi: 10.3390/nu10101398.
34. Chistiakov D.A., Bobryshev Y.V., Kozarov E., Sobenin I.A., Orekhov A.N. Role of gut microbiota in the modulation of atherosclerosis-associated immune response. Front Microbiol. 2015 Jun 30;6:671. doi: 10.3389/fmicb.2015.00671.
35. Ross R., Glomset J.A. Atherosclerosis and the arterial smooth muscle cell. Science. 1973;180 (4093):1332-1339. doi: 10.1126/science.180.4093.1332.
36. Koeth R.A., Wang Z., Levison B.S., Buffa J.A., Org E., Sheehy B.T.Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013;19 (5):576-585. doi: 10.1038/nm.3145.
37. Ding L., Chang M., Guo Y., Zhang L., Xue C., Yanagita T. Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism. Lipids Health Dis. 2018;17 (1):286. doi: 10.1186/s12944-018-0939-6.
38. Warrier M., Shih D.M., Burrows A.C., Ferguson D., Gromovsky A.D., Brown A.L. The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance. Cell Rep. 2015;10 (3):326-338. doi: 10.1016/j.celrep.2014.12.036.
39. Al-Rubaye H., Perfetti G., Kaski J.C. The Role of Microbiota in Cardiovascular Risk: Focus on Trimethylamine Oxide. Curr. Probl Cardiol. 2019;44 (6):182-196. doi: 10.1016/j.cpcardiol.2018.06.005.
40. Chiang J.Y., Kimmel R., Stroup D. Regulation of cholesterol 7α-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXRα). Gene. 2001;262 (1-2):257-265. doi: 10.1016/s0378-1119(00)00518-7.
41. Warrier M., Shih D.M., Burrows A.C., Ferguson D., Gromovsky A.D., Brown A.L. The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of Cholesterol Balance. Cell Rep. 2015;10 (3):326-338. doi: 10.1016/j.celrep.2014.12.036.
42. Chen K., Febbraio M., Li W., Silverstein R.L. A specific CD36-dependent signaling pathway is required for platelet activation by oxidized low-density lipoprotein. Circ. Res. 2008;102 (12):1512-1519. doi: 10.1161/circresaha.108.172064.
43. Zhu W., Wang Z., Tang W.H.W., Hazen S.L. Gut microbe-generated trimethylamine N-Oxide from dietary choline is prothrombotic in subjects. Circulation. 2017;135 (17):1671-1673. doi: 10.1161/circulationaha.116.025338.
44. Frossard, M., Fuchs, I., Leitner, J. M., Hsieh, K., Vlcek, M., Losert, H. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation. 2004;110 (11):1392-1397. doi: 10.1161/01.CIR.0000141575.92958.9C.
45. Zhu W., Gregory J.C., Org E., Buffa J.A., Gupta N., Wang Z. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016;165 (1):111-124. doi: 10.1016/j.cell.2016.02.011.
46. Yang M., Kholmukhamedov A., Schulte M.L., Cooley B.C., Scoggins N.O., Wood J.P. Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo. Blood Adv. 2018: 2 (21): 2848-2861. doi: 10.1182/bloodadvances.2018025411.
47. Wu X., Chen L., Zeb F., Huang Y., An J., Ren J. Regulation of circadian rhythms by NEAT1 mediated TMAO-induced endothelial proliferation: A protective role of asparagus extract. Exp. Cell Res. 2019;382 (1):111451. doi: 10.1016/j.yexcr.2019.05.032.
48. Cheng X., Qiu X., Liu Y., Yuan C., Yang X. Trimethylamine N-oxide promotes tissue factor expression and activity in vascular endothelial cells: A new link between trimethylamine N-oxide and atherosclerotic thrombosis. Thromb. Res. 2019;177:110-116. doi: 10.1016/j.thromres.2019.02.028.
49. Seldin M.M., Meng Y., Qi H., Zhu W., Wang Z., Hazen S.L. Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-kappaB. J. Am. Heart Assoc. 2016;5 (2): e002767. doi: 10.1161/jaha.115.002767.
50. Skye S.M., Zhu W., Romano K.A., Guo C.J., Wang Z., Jia X. Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential. Circ. Res. 2018;123 (10):1164-1176. doi: 10.1161/circresaha.118.313142.
51. Roberts A.B., Gu X., Buffa J.A., Hurd A.G., Wang Z., Zhu W. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med. 2018;24 (9):1407-1417. doi: 10.1038/s41591-018-0128-1.
52. Shih D.M., Zhu W., Schugar R.C., Meng Y., Jia X., Miikeda A. Genetic Deficiency of Flavin-Containing Monooxygenase-3 (Fmo3) Protects Against Thrombosis but Has Only a Minor Effect on Plasma Lipid Levels. Arterioscler. Thromb. Vasc. Biol. 2019; 39 (6):1045-1054. doi: 10.1161/atvbaha.119.312592.
53. van Mens T.E., Buller H.R., Nieuwdorp M. Targeted inhibition of gut microbiota proteins involved in TMAO production to reduce platelet aggregation and arterial thrombosis: a blueprint for drugging the microbiota in the treatment of cardiometabolic disease? J. Thromb. Haemost. 2019;17 (1):3-5. doi: 10.1111/jth.14331.
54. Brusca S.B., Abramson S.B., Scher J.U. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr. Opin. Rheumatol. 2014;26:101-107.
55. Scher J.U., Sczesnak A., Longman R.S. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013;2: e01202.
56. Vaahtovuo J., Munukka E., Korkeamäki M., Luukkainen R., Toivanen P. Fecal microbiota in early rheumatoid arthritis. J. Rheumatol. 2008;35:1500-1505.
57. Chung Y.-L., Rider L.G., Bell J.D. et al. Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies. Arthritis Rheum. 2005, 53, 565-570.
58. Myers L.K., Rosloniec E.F., Cremer M.A., Kang A.H. Collagen-induced arthritis, an animal model of autoimmunity. Life Sci. 1997;61:1861-1878.
59. Lin K.M., Chen W.M., Tung S.Y. et al. Prevalence and Predictive Value of High-Positive Rheumatoid Factor and Anti-Citrullinated Protein Antibody Levels in Nonarthritic Patients with Chronic Hepatitis C Infection.Int. J. Rheum. Dis. 2019;22:116-120.
60. Geraldino-Pardilla L., Giles J.T., Sokolove J. et al. Association of Anti-Citrullinated Peptide Antibodies with Coronary Artery Calcification in Rheumatoid Arthritis. Arthritis Rheum. 2017;69:1276-1281.
61. Okano T., Inui K., Sugioka Y. et al. High titer of anti-citrullinated peptide antibody is a risk factor for severe carotid atherosclerotic plaque in patients with rheumatoid arthritis: The TOMORROW study.Int. J. Rheum. Dis. 2017;20:949-959.
62. György B., Tóth E., Tarcsa E., Falus A., Buzás E.I. Citrullination: A posttranslational modification in health and disease.Int. J. Biochem. Cell Biol. 2006;38:1662-1677.
63. Van Venrooij W.J., Pruijn G.J. How citrullination invaded rheumatoid arthritis research. Arthritis Res. Ther. 2014;16:103.
64. McInnes I.B., Schett G. The Pathogenesis of Rheumatoid Arthritis. N. Engl. J. Med. 2011;365:2205-2219.
65. Dragoljevic D., Kraakman M.J., Nagareddy P.R. et al. Defective cholesterol metabolism in haematopoietic stem cells promotes monocyte-driven atherosclerosis in rheumatoid arthritis. Eur. Heart J. 2018;39:2158-2167.
66. Archer A.M., Saber R., Rose S. et al. ApoE deficiency exacerbates the development and sustainment of a semi-chronic K/BxN serum transfer-induced arthritis model. J. Transl. Med. 2016;14:170.
67. 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. J. Am. Heart Assoc. 2016;5: e002767.
68. Habets K.L., Trouw L.A., Levarht E.N. et al. Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis. Arthritis Res. Ther. 2015;17:209.
69. Chung W.S., Peng C.L., Lin C.L. et al. Rheumatoid Arthritis Increases the Risk of Deep Vein Thrombosis and Pulmonary Thromboembolism: A Nationwide Cohort Study. Ann. Rheum. Dis. 2014;73:1774-1780.
70. Masoud S., Lim P.B., Kitas G.D., Panoulas V. Sudden cardiac death in patients with rheumatoid arthritis. World J. Cardiol. 2017;9:562-573.
71. Wu W.-K., Panyod S., Ho C.-T., Kuo C.-H., Wu M.-S., Sheen L.-Y. Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota. J. Funct. Foods. 2015;15:408-417.
72. Chen M.-L., Yi L., Zhang Y. et al. Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota. mBio. 2016;7: e02210-15.
73. Bresciani L., Dall’Asta M., Favari C., Calani L., Del Rio D., Brighenti F. An in vitro exploratory study of dietary strategies based on polyphenol-rich beverages, fruit juices and oils to control trimethylamine production in the colon. Food Funct. 2018;9:6470-6483.
74. Qiu L., Yang D., Tao X., Yu J., Xiong H., Wei H. Enterobacter Aerogenes ZDY01 Attenuates Choline-Induced Trimethylamine N-Oxide Levels by Remodeling Gut Microbiota in Mice. J. Microbiol. Biotechnol. 2017;27:1491-1499.
Рецензия
Для цитирования:
Тарасова Л.В., Кокурина К.А., Цыганова Ю.В. Триметиламин- N-оксид (ТМАО) в патогенезе ревматоидного артрита и сердечно- сосудистых осложнений. Экспериментальная и клиническая гастроэнтерология. 2025;(12):127-134. https://doi.org/10.31146/1682-8658-ecg-244-12-127-134
For citation:
Tarasova L.V., Kokurina K.A., Tsyganova Yu.V. Trimethylamine- N-oxide (TMAO) in the pathogenesis of rheumatoid arthritis and cardiovascular complications. Experimental and Clinical Gastroenterology. 2025;(12):127-134. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-244-12-127-134
Просмотров:
377
JATS XML
Послать статью по эл. почте 
