Фактор роста фибробластов 21 (FGF21): диагностические, прогностические и терапевтические аспекты при сердечной недостаточности

1. Lee J, Oh O, Park DI, et al. Scoping review of measures of comorbidities in heart failure. J Cardiovasc Nurs. 2024;39(1):5-17. DOI:10.1097/JCN.0000000000001016 
2. Doherty DJ, Docherty KF, Gardner RS. Review of the National Institute for Health and Care Excellence guidelines on chronic heart failure. Heart. 2024;110(7):466-75. DOI:10.1136/heartjnl-2022-322164 
3. Калюжин В.В., Тепляков А.Т., Черногорюк Г.Э., и др. Хроническая сердечная недостаточность: синдром или заболевание? Бюллетень сибирской медицины. 2020;19(1):134-9 [Kalyuzhin VV, Teplyakov AT, Chernogoryuk GE, et al. Chronic heart failure: syndrome or disease? Bulletin of Siberian Medicine. 2020;19(1):134-9 (in Russian)]. DOI:10.20538/1682-0363-2020-1-134-139
4. Kretzschmar T, Westphal J, Neugebauer S, et al. Metabolic profiling identifies 1-MetHis and 3-IPA as potential diagnostic biomarkers for patients with acute and chronic heart failure with reduced ejection fraction. Circ Heart Fail. 2024;17(1):e010813. DOI:10.1161/CIRCHEARTFAILURE.123.010813 
5. Голухова Е.З., Теряева Н.Б., Алиева А.М. Натрийуретические пептиды – маркеры и факторы прогноза при хронической сердечной недостаточности. Креативная кардиология.2007;1-2:126-36 [Golukhova EZ, Teryaeva NB, Alieva AM. Natriuretic peptides: markers and prognostic factors in chronic heart failure. Creative Cardiology.
2007;1-2:126-36 (in Russian)].
6. Голухова Е.З., Алиева А.М. Клиническое значение определения натрийуретических пептидов у больных с хронической сердечной недостаточностью. Кардиология и сердечно-сосудистая хирургия. 2007;47(1):45-51 [Golukhova EZ, Alieva AM. Clinical value of natriuretic peptides detection at the patients with chronic heart failure. The Russian Journal of Cardiology & Cardiovascular Surgery. 2007;47(1):45-51 (in Russian)].
7. Goutam RS, Kumar V, Lee U, Kim J. Exploring the structural and functional diversity among FGF signals: A comparative study of human, mouse, and xenopus FGF ligands in embryonic development and cancer pathogenesis. Int J Mol Sci. 2023;24(8):7556. DOI:10.3390/ijms24087556 
8. Yan J, Nie Y, Cao J, et al. The roles and pharmacological effects of FGF21 in preventing aging-associated metabolic diseases. Front Cardiovasc Med. 2021;8:655575. DOI:10.3389/fcvm.2021.655575
9. Shao W, Jin T. Hepatic hormone FGF21 and its analogues in clinical trials. Chronic Dis Transl Med. 2022;8(1):19-25. DOI:10.1016/j.cdtm.2021.08.005 
10. Badakhshi Y, Jin T. Current understanding and controversies on the clinical implications of fibroblast growth factor 21. Crit Rev Clin Lab Sci. 2021;58(5):311-28. DOI:10.1080/10408363.2020.1864278
11. Falamarzi K, Malekpour M, Tafti MF, et al. The role of FGF21 and its analogs on liver associated diseases. Front Med (Lausanne). 2022;9:967375. DOI:10.3389/fmed.2022.967375
12. Алиева А.М., Байкова И.Е., Резник Е.В., и др. Фактор роста фибробластов 21-новый инструмент в многокомпонентной оценке сердечно-сосудистых заболеваний. Российский медицинский журнал. 2022;28(1):75-88 [Alieva AM, Baikova IE, Reznik EV, et al. Fibroblast growth factor 21 as a new tool in the multicomponent assessment of cardiovascular diseases. Russian Medicine. 2022;28(1):75-88 (in Russian)]. DOI:10.17816/medjrf108900
13. Aaldijk AS, Verzijl CRC, Jonker JW, Struik D. Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho. Front Endocrinol (Lausanne). 2023;14:1150222. DOI:10.3389/fendo.2023.1150222 
14. Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115(6):1627-35. DOI:10.1172/JCI23606
15. Cuevas-Ramos D, Mehta R, Aguilar-Salinas CA. Fibroblast growth factor 21 and browning of white adipose tissue. Front Physiol. 2019;10:37. DOI:10.3389/fphys.2019.00037 
16. Holland WL, Adams AC, Brozinick JT, et al. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab. 2013;17(5):790-7. DOI:10.1016/j.cmet.2013.03.019
17. Wente W, Efanov AM, Brenner M, et al. Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes. 2006;55(9):2470-8. DOI:10.2337/db05-1435
18. Rosales-Soto G, Diaz-Vegas A, Casas M, et al. Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers. J Mol Endocrinol. 2020:JME-19-0210.R2. DOI:10.1530/JME-19-0210
19. Tucker W, Tucker B, Rye KA, Ong KL. Fibroblast growth factor 21 in heart failure. Heart Fail Rev. 2023;28(1):261-72. DOI:10.1007/s10741-022-10268-0 
20. Sarruf DA, Thaler JP, Morton GJ, et al. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes. 2010;59(7):1817-24. DOI:10.2337/db09-1878
21. Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 2014;20(4):670-7. DOI:10.1016/j.cmet.2014.07.012
22. Fisher FM, Chui PC, Antonellis PJ, et al. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010;59(11):2781-9. DOI:10.2337/db10-0193
23. Geng L, Liao B, Jin L, et al. Exercise alleviates obesity-induced metabolic dysfunction via enhancing FGF21 sensitivity in adipose tissues. Cell Rep. 2019;26(10):2738-52.e4. DOI:10.1016/j.celrep.2019.02.014 
24. Planavila A, Redondo I, Hondares E, et al. Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun. 2013;4:2019. DOI:10.1038/ncomms3019 
25. Planavila A, Redondo-Angulo I, Ribas F, et al. Fibroblast growth factor 21 protects the heart from oxidative stress. Cardiovasc Res. 2015;106(1):19-31. DOI:10.1093/cvr/cvu263 
26. Joki Y, Ohashi K, Yuasa D, et al. FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism. Biochem Biophys Res Commun. 2015;459(1):124-30. DOI:10.1016/j.bbrc.2015.02.081 
27. Planavila A, Redondo-Angulo I, Villarroya F. FGF21 and cardiac physiopathology. Front Endocrinol (Lausanne). 2015;6:133. DOI:10.3389/fendo.2015.00133 
28. Rius-Pérez S, Torres-Cuevas I, Millán I, et al. PGC-1α, inflammation, and oxidative stress: an integrative view in metabolism. Oxid Med Cell Longev. 2020;2020:1452696. DOI:10.1155/2020/1452696
29. Pan X, Shao Y, Wu F, et al. FGF21 prevents angiotensin II-induced hypertension and vascular dysfunction by activation of ACE2/angiotensin-(1-7) axis in mice. Cell Metab. 2018;27(6):1323-37.e5. DOI:10.1016/j.cmet.2018.04.002
30. Huang Z, Xu A, Cheung BMY. The potential role of fibroblast growth factor 21 in lipid metabolism and hypertension. Curr Hypertens Rep. 2017;19(4):28.
DOI:10.1007/s11906-017-0730-5 
31. Yang M, Liu C, Jiang N, et al. Fibroblast growth factor 21 in metabolic syndrome. Front Endocrinol (Lausanne). 2023;14:1220426. DOI:10.3389/fendo.2023.1220426
32. Wang N, Xu TY, Zhang X, et al. Improving hyperglycemic effect of FGF-21 is associated with alleviating inflammatory state in diabetes. Int Immunopharmacol. 2018;56:301-9. DOI:10.1016/j.intimp.2018.01.048 
33. Furukawa N, Koitabashi N, Matsui H, et al. DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism. Heart Vessels. 2021;36(1):136-46. DOI:10.1007/s00380-020-01711-z
34. Chou RH, Huang PH, Hsu CY, et al. Circulating fibroblast growth factor 21 is associated with diastolic dysfunction in heart failure patients with preserved ejection fraction. Sci Rep. 2016;6:33953. DOI:10.1038/srep33953
35. Fan L, Gu L, Yao Y, Ma G. Elevated serum fibroblast growth factor 21 is relevant to heart failure patients with reduced ejection fraction. Comput Math Methods Med. 2022;2022:7138776. DOI:10.1155/2022/7138776
36. Sommakia S, Almaw NH, Lee SH, et al. FGF21 (fibroblast growth factor 21) defines a potential cardiohepatic signaling circuit in end-stage heart failure. Circ Heart Fail. 2022;15(3):e008910. DOI:10.1161/CIRCHEARTFAILURE.121.008910
37. Ianoș RD, Pop C, Iancu M, et al. Diagnostic performance of serum biomarkers fibroblast growth factor 21, galectin-3 and copeptin for heart failure with preserved ejection fraction in a sample of patients with type 2 diabetes mellitus. Diagnostics (Basel). 2021;11(9):1577. DOI:10.3390/diagnostics11091577
38. Gu L, Jiang W, Zheng R, et al. Fibroblast growth factor 21 correlates with the prognosis of dilated cardiomyopathy. Cardiology. 2021;146(1):27-33. DOI:10.1159/000509239 
39. Gu L, Jiang W, Jiang W, et al. Elevated serum FGF21 levels predict heart failure during hospitalization of STEMI patients after emergency percutaneous coronary intervention. Peer J. 2023;11:e14855. DOI:10.7717/peerj.14855
40. Yan B, Ma S, Yan C, Han Y. Fibroblast growth factor 21 and prognosis of patients with cardiovascular disease: A meta-analysis. Front Endocrinol (Lausanne). 2023;14:1108234. DOI:10.3389/fendo.2023.1108234

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1. Lee J, Oh O, Park DI, et al. Scoping review of measures of comorbidities in heart failure. J Cardiovasc Nurs. 2024;39(1):5-17. DOI:10.1097/JCN.0000000000001016 
2. Doherty DJ, Docherty KF, Gardner RS. Review of the National Institute for Health and Care Excellence guidelines on chronic heart failure. Heart. 2024;110(7):466-75. DOI:10.1136/heartjnl-2022-322164 
3. Kalyuzhin VV, Teplyakov AT, Chernogoryuk GE, et al. Chronic heart failure: syndrome or disease? Bulletin of Siberian Medicine. 2020;19(1):134-9 (in Russian).
DOI:10.20538/1682-0363-2020-1-134-139
4. Kretzschmar T, Westphal J, Neugebauer S, et al. Metabolic profiling identifies 1-MetHis and 3-IPA as potential diagnostic biomarkers for patients with acute and chronic heart failure with reduced ejection fraction. Circ Heart Fail. 2024;17(1):e010813. DOI:10.1161/CIRCHEARTFAILURE.123.010813 
5. Golukhova EZ, Teryaeva NB, Alieva AM. Natriuretic peptides: markers and prognostic factors in chronic heart failure. Creative Cardiology. 2007;1-2:126-36 (in Russian).
6. Golukhova EZ, Alieva AM. Clinical value of natriuretic peptides detection at the patients with chronic heart failure. The Russian Journal of Cardiology & Cardiovascular Surgery. 2007;47(1):45-51 (in Russian).
7. Goutam RS, Kumar V, Lee U, Kim J. Exploring the structural and functional diversity among FGF signals: A comparative study of human, mouse, and xenopus FGF ligands in embryonic development and cancer pathogenesis. Int J Mol Sci. 2023;24(8):7556. DOI:10.3390/ijms24087556 
8. Yan J, Nie Y, Cao J, et al. The roles and pharmacological effects of FGF21 in preventing aging-associated metabolic diseases. Front Cardiovasc Med. 2021;8:655575. DOI:10.3389/fcvm.2021.655575
9. Shao W, Jin T. Hepatic hormone FGF21 and its analogues in clinical trials. Chronic Dis Transl Med. 2022;8(1):19-25. DOI:10.1016/j.cdtm.2021.08.005 
10. Badakhshi Y, Jin T. Current understanding and controversies on the clinical implications of fibroblast growth factor 21. Crit Rev Clin Lab Sci. 2021;58(5):311-28. DOI:10.1080/10408363.2020.1864278
11. Falamarzi K, Malekpour M, Tafti MF, et al. The role of FGF21 and its analogs on liver associated diseases. Front Med (Lausanne). 2022;9:967375. DOI:10.3389/fmed.2022.967375
12. Alieva AM, Baikova IE, Reznik EV, et al. Fibroblast growth factor 21 as a new tool in the multicomponent assessment of cardiovascular diseases. Russian Medicine. 2022;28(1):75-88 (in Russian). DOI:10.17816/medjrf108900
13. Aaldijk AS, Verzijl CRC, Jonker JW, Struik D. Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho. Front Endocrinol (Lausanne). 2023;14:1150222. DOI:10.3389/fendo.2023.1150222 
14. Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115(6):1627-35. DOI:10.1172/JCI23606
15. Cuevas-Ramos D, Mehta R, Aguilar-Salinas CA. Fibroblast growth factor 21 and browning of white adipose tissue. Front Physiol. 2019;10:37. DOI:10.3389/fphys.2019.00037 
16. Holland WL, Adams AC, Brozinick JT, et al. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab. 2013;17(5):790-7. DOI:10.1016/j.cmet.2013.03.019
17. Wente W, Efanov AM, Brenner M, et al. Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes. 2006;55(9):2470-8. DOI:10.2337/db05-1435
18. Rosales-Soto G, Diaz-Vegas A, Casas M, et al. Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers. J Mol Endocrinol. 2020:JME-19-0210.R2. DOI:10.1530/JME-19-0210
19. Tucker W, Tucker B, Rye KA, Ong KL. Fibroblast growth factor 21 in heart failure. Heart Fail Rev. 2023;28(1):261-72. DOI:10.1007/s10741-022-10268-0 
20. Sarruf DA, Thaler JP, Morton GJ, et al. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes. 2010;59(7):1817-24. DOI:10.2337/db09-1878
21. Owen BM, Ding X, Morgan DA, et al. FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. Cell Metab. 2014;20(4):670-7. DOI:10.1016/j.cmet.2014.07.012
22. Fisher FM, Chui PC, Antonellis PJ, et al. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010;59(11):2781-9. DOI:10.2337/db10-0193
23. Geng L, Liao B, Jin L, et al. Exercise alleviates obesity-induced metabolic dysfunction via enhancing FGF21 sensitivity in adipose tissues. Cell Rep. 2019;26(10):2738-52.e4. DOI:10.1016/j.celrep.2019.02.014 
24. Planavila A, Redondo I, Hondares E, et al. Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat Commun. 2013;4:2019. DOI:10.1038/ncomms3019 
25. Planavila A, Redondo-Angulo I, Ribas F, et al. Fibroblast growth factor 21 protects the heart from oxidative stress. Cardiovasc Res. 2015;106(1):19-31. DOI:10.1093/cvr/cvu263 
26. Joki Y, Ohashi K, Yuasa D, et al. FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism. Biochem Biophys Res Commun. 2015;459(1):124-30. DOI:10.1016/j.bbrc.2015.02.081 
27. Planavila A, Redondo-Angulo I, Villarroya F. FGF21 and cardiac physiopathology. Front Endocrinol (Lausanne). 2015;6:133. DOI:10.3389/fendo.2015.00133 
28. Rius-Pérez S, Torres-Cuevas I, Millán I, et al. PGC-1α, inflammation, and oxidative stress: an integrative view in metabolism. Oxid Med Cell Longev. 2020;2020:1452696. DOI:10.1155/2020/1452696
29. Pan X, Shao Y, Wu F, et al. FGF21 prevents angiotensin II-induced hypertension and vascular dysfunction by activation of ACE2/angiotensin-(1-7) axis in mice. Cell Metab. 2018;27(6):1323-37.e5. DOI:10.1016/j.cmet.2018.04.002
30. Huang Z, Xu A, Cheung BMY. The potential role of fibroblast growth factor 21 in lipid metabolism and hypertension. Curr Hypertens Rep. 2017;19(4):28.
DOI:10.1007/s11906-017-0730-5 
31. Yang M, Liu C, Jiang N, et al. Fibroblast growth factor 21 in metabolic syndrome. Front Endocrinol (Lausanne). 2023;14:1220426. DOI:10.3389/fendo.2023.1220426
32. Wang N, Xu TY, Zhang X, et al. Improving hyperglycemic effect of FGF-21 is associated with alleviating inflammatory state in diabetes. Int Immunopharmacol. 2018;56:301-9. DOI:10.1016/j.intimp.2018.01.048 
33. Furukawa N, Koitabashi N, Matsui H, et al. DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism. Heart Vessels. 2021;36(1):136-46. DOI:10.1007/s00380-020-01711-z
34. Chou RH, Huang PH, Hsu CY, et al. Circulating fibroblast growth factor 21 is associated with diastolic dysfunction in heart failure patients with preserved ejection fraction. Sci Rep. 2016;6:33953. DOI:10.1038/srep33953
35. Fan L, Gu L, Yao Y, Ma G. Elevated serum fibroblast growth factor 21 is relevant to heart failure patients with reduced ejection fraction. Comput Math Methods Med. 2022;2022:7138776. DOI:10.1155/2022/7138776
36. Sommakia S, Almaw NH, Lee SH, et al. FGF21 (fibroblast growth factor 21) defines a potential cardiohepatic signaling circuit in end-stage heart failure. Circ Heart Fail. 2022;15(3):e008910. DOI:10.1161/CIRCHEARTFAILURE.121.008910
37. Ianoș RD, Pop C, Iancu M, et al. Diagnostic performance of serum biomarkers fibroblast growth factor 21, galectin-3 and copeptin for heart failure with preserved ejection fraction in a sample of patients with type 2 diabetes mellitus. Diagnostics (Basel). 2021;11(9):1577. DOI:10.3390/diagnostics11091577
38. Gu L, Jiang W, Zheng R, et al. Fibroblast growth factor 21 correlates with the prognosis of dilated cardiomyopathy. Cardiology. 2021;146(1):27-33. DOI:10.1159/000509239 
39. Gu L, Jiang W, Jiang W, et al. Elevated serum FGF21 levels predict heart failure during hospitalization of STEMI patients after emergency percutaneous coronary intervention. Peer J. 2023;11:e14855. DOI:10.7717/peerj.14855
40. Yan B, Ma S, Yan C, Han Y. Fibroblast growth factor 21 and prognosis of patients with cardiovascular disease: A meta-analysis. Front Endocrinol (Lausanne). 2023;14:1108234. DOI:10.3389/fendo.2023.1108234

А.М. Алиева*¹, Н.В. Теплова¹, Е.В. Резник¹, И.Е. Байкова¹, Н.Х. Хаджиева², К.В. Воронкова¹, И.В. Ковтюх¹, Р.К. Валиев³, И.А. Котикова¹, И.Г. Никитин<sup>1

1</sup>ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
²Клиника Генетики и ДНК «МедЭстет», Москва, Россия;
³ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия
*amisha_alieva@mail.ru

________________________________________________

Amina M. Alieva*¹, Natalia V. Teplova¹, Elena V. Reznik¹, Irina E. Baykova¹, Nyurzhanna Kh. Khadzhieva², Kira V. Voronkova¹, Irina V. Kovtiukh¹, Ramiz K. Valiev³, Irina A. Kotikova¹, Igor G. Nikitin<sup>1

1</sup>Pirogov Russian National Research Medical University, Moscow, Russia;
²MedEstet Genetics and DNA Clinic, Moscow, Russia;
³Loginov Moscow Clinical Scientific Center, Moscow, Russia
*amisha_alieva@mail.ru