Фактор роста нервных клеток и постинфарктное ремоделирование сердца

Распространённость внезапной смерти от хронической сердечной недостаточности и аритмий, вызванных инфарктом миокарда, является сложной проблемой кардиологии. После перенесенного инфаркта миокарда запускается процесс ремоделирования сердца – известный как компенсаторно-приспособительная реакция, включающая в себя изменения структуры и функции кардиомиоцитов, стромальных элементов и внеклеточного матрикса, геометрии и архитектоники полости левого желудочка, которые регулируются механическими, нейрогуморальными и генетическими факторами. Неблагоприятное ремоделирование левого желудочка связано с развитием сердечной недостаточности и повышенной смертностью. Концепция постинфарктного ремоделирования сердца является актуальным вопросом медицины, так как механизмы развития и прогрессирования неблагоприятных постинфарктных изменений в миокарде полностью не определены. В последние годы внимание учёных приковано к нейротрофическим факторам, вовлечённым в процессы ремоделирования симпатической нервной системы и сосудистой системы после перенесённого инфаркта миокарда. Фактор роста нервов (NGF, nerve growth factor) – белок из семейства нейротрофинов, необходимый для выживания и развития симпатических и сенсорных нейронов, который также играет важную роль в васкулогенезе. Острый инфаркт миокарда и сердечная недостаточность характеризуются изменениями в экспрессии и активности нейротрофических факторов и их рецепторов, что оказывает влияние на иннервацию сердечной мышцы, а также прямое воздействие на кардиомиоциты, эндотелиальные и гладкомышечные сосудистые клетки. Идентификация молекулярных механизмов, участвующих во взаимодействиях между кардиомиоцитами и нейронами, а также изучение эффектов, оказываемых NGF в сердечно-сосудистой системе, поможет улучшить понимание процесса ремоделирования сердца. Данный обзор обобщает имеющуюся в литературе информацию (2019–2021 гг.), посвящённую патофизиологическим и патогенетическим механизмам взаимосвязи процессов ремоделирования миокарда и функций NGF в сердечно-сосудистой системе.

1. Virani SS, Alonso А, Benjamin EJ. Heart disease and stroke statistics-2020 update: A report from the American Heart Association. Circulation. 2020; 141(9): 139-596. doi: 10.1161/CIR.0000000000000757

2. Shih J-Y, Chen Z-C, Chang H-Y. Risks of age and sex on clinical outcomes post myocardial infarction. Int J Cardiol Heart Vasc. 2019; 23: 100350. doi: 10.1016/j.ijcha.2019.100350

3. Report on cardiovascular health and diseases in China 2019: An updated summary. Chinese Circulation Journal. 2020; 35(9): 833-854.

4. Timmis A, Townsend N, Gale CP. European Society of Cardiology: Cardiovascular disease statistics 2019. Eur Heart J. 2020; 41: 12-85. doi: 10.1093/eurheartj/ehz859

5. Maglietta G, Ardissino М, Malagoli Tagliazucchi G. Longterm outcomes after early-onset myocardial infarction. J Am Coll Cardiol. 2019; 74(16): 2113-2115. doi: 10.1016/j.jacc.2019.08.1000

6. Pfeffer MA. Survival after an experimental myocardial infarction: Beneficial effects of long-term therapy with captopril. Circulation. 1985; 2(72): 406-412.

7. Guo Y, Zhang C, Ye T, Chen X, Liu X, Chen X, et al. Pinocembrin ameliorates arrhythmias in rats with chronic ischaemic heart failure. Ann Med. 2021; 53(1): 830-840. doi: 10.1080/07853890.2021.1927168

8. Wu Y, Liu H, Wang X. Cardioprotection of pharmacological postconditioning on myocardial ischemia/reperfusion injury. Life Sci. 2021; 264: 118628. doi: 10.1016/j.lfs.2020.118628

9. Maida CD, Norrito RL, Daidone M. Neuroinflammatory mechanisms in ischemic stroke: Focus on cardioembolic stroke, background, and therapeutic approaches. Int J Mol Sci. 2020; 21(18): 6454. doi: 10.3390/ijms21186454

10. Morton AB, Jacobsen NL, Segal SS. Functionalizing biomaterials to promote neurovascular regeneration following skeletal muscle injury. Am J Physiol Cell Physiol. 2021; 320(6): C1099-C1111. doi: 10.1152/ajpcell.00501.2020

11. Gonçalves RC, Banfi A, Oliveira MB. Strategies for revascularization and promotion of angiogenesis in trauma and disease. Biomaterials. 2021; 269: 120628. doi: 10.1016/j.biomaterials.2020.120628

12. László A, Lénárt L, Illésy L. The role of neurotrophins in psychopathology and cardiovascular diseases: Psychosomatic connections. J Neural Transm (Vienna). 2019; 126(3): 265-278. doi: 10.1007/s00702-019-01973-6

13. Kotlega D, Zembron-Lacny A, Morawin B. Free fatty acids and their inflammatory derivatives affect BDNF in stroke patients. Mediators Inflamm. 2020; 2020: 6676247. doi: 10.1155/2020/6676247

14. Jamali A, Shahrbanian S, Morteza Tayebi S. The effects of exercise training on the brain-derived neurotrophic factor (BDNF) in the patients with type 2 diabetes: A systematic review of the randomized controlled trials. J Diabetes Metab Disord. 2020; 19(1): 633-643. doi: 10.1007/s40200-020-00529-w

15. Wang J, Amidfar M, Eyileten C. Nerve growth factor in metabolic complications and Alzheimer’s disease: Physiology and therapeutic potential. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10): 165858. doi: 10.1016/j.bbadis.2020.165858

16. Xue Y, Liang H, Yang R. The role of pro- and mature neurotrophins in the depression. Behav Brain Res. 2021; 404: 113162. doi: 10.1016/j.bbr.2021.113162

17. Hang PZ, Zhu H, Li PF. The emerging role of BDNF/TrkB signaling in cardiovascular diseases. Life (Basel). 2021; 11(1): 70. doi: 10.3390/life11010070

18. Halloway S, Jung M, Yeh AY. An integrative review of brain-derived neurotrophic factor and serious cardiovascular conditions. Nurs Res. 2020; 69(5): 376-390. doi: 10.1097/NNR.0000000000000454

19. Wise BL, Seidel MF, Lane NE. The evolution of nerve growth factor inhibition in clinical medicine. Nat Rev Rheumatol. 2021; 17(1): 34-46. doi: 10.1038/s41584-020-00528-4

20. Pius-Sadowska E, Machaliński B. Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis. ESC Heart Fail. 2021; 8(2): 974-987. doi: 10.1002/ehf2.13138

21. Li R, Xu J, Rao Z. Facilitate angiogenesis and neurogenesis by growth factors integrated decellularized matrix hydrogel. Tissue Eng Part A. 2021; 27(11-12): 771-787. doi: 10.1089/ten.TEA.2020.0227

22. Yan T, Zhang Z, Li D. NGF receptors and PI3K/AKT pathway involved in glucose fluctuation-induced damage to neurons and alpha-lipoic acid treatment. BMC Neuroscience. 2020; 21(1): 38. doi: 10.1186/s12868-020-00588-y

23. Xu F, Na L, Li Y. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci. 2020; 10: 54. doi: 10.1186/s13578-020-00416-0

24. Baldassarro VA, Lorenzini L, Bighinati A. NGF and endogenous regeneration: From embryology toward therapies. Adv Exp Med Biol. 2021; 1331: 51-63. doi: 10.1007/978-3-030-74046-7_5

25. Dahlström M, Nordvall G, Sundström E. Identification of amino acid residues of nerve growth factor important for neurite outgrowth in human dorsal root ganglion neurons. Eur J Neurosci. 2019; 50: 3487-3501. doi: 10.1111/ejn.14513

26. Testa G, Cattaneo A, Capsoni S. Understanding pain perception through genetic painlessness diseases: The role of NGF and proNGF. Pharmacol Res. 2021; 169: 105662. doi: 10.1016/j.phrs.2021.105662

27. Grassi G, Quarti-Trevano F, Esler MD. Sympathetic activation in congestive heart failure: An updated overview. Heart Fail Rev. 2021; 26(1): 173-182. doi: 10.1007/s10741-019-09901-2

28. Ceci FM, Ferraguti G, Petrella C, Greco A, Tirassa P, Iannitelli A, et al. Nerve growth factor, stress and diseases. Curr Med Chem. 2021; 28(15): 2943-2959. doi: 10.2174/0929867327999200818111654

29. Wang Y, Tan J, Yin J, Hu H, Shi Y, Wang Y, et al. Targeting blockade of nuclear factor-kappaB in the hypothalamus paraventricular nucleus to prevent cardiac sympathetic hyperinnervation post myocardial infarction. Neurosci Lett. 2019; 707: 134319. doi: 10.1016/j.neulet.2019.134319

30. Oliveira ÍM, Silva Júnior ELD, Martins YO, Rocha HAL, Scanavacca MI, Gutierrez PS. Cardiac autonomic nervous system remodeling may play a role in atrial fibrillation: A study of the autonomic nervous system and myocardial receptors. Arq Bras Cardiol. 2021; 117(5): 999-1007. doi: 10.36660/abc.20200725

31. Gussak G, Pfenniger A, Wren L, Gilani M, Zhang W, Yoo S, et al. Region-specific parasympathetic nerve remodeling in the left atrium contributes to creation of a vulnerable substrate for atrial fibrillation. JCI Insight. 2019; 4(20): e130532. doi: 10.1172/jci.insight.130532

32. Yang M, Zhang S, Liang J, Tang Y, Wang X, Huang C, et al. Different effects of norepinephrine and nerve growth factor on atrial fibrillation vulnerability. J Cardiol. 2019; 74: 460-465. doi: 10.1016/j.jjcc.2019.04.009

33. Wang Z, Li S, Lai H, Zhou L, Meng G, Wang M, et al. Interaction between endothelin-1 and left stellate ganglion activation: A potential mechanism of malignant ventricular arrhythmia during myocardial ischemia. Oxid Med Cell Longev. 2019; 2019: 6508328. doi: 10.1155/2019/6508328

34. Jie X, Yang H, Wang K, Zhu ZF, Wang JP, Yang LG, et al. Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure. Clin Exp Pharmacol Physiol. 2021; 48(5): 704-716. doi: 10.1111/1440-1681.13465

35. Cheng XY, Chen C, He SF, Huang CX, Zhang L, Chen ZW, et al. Spinal NGF induces anti-intrathecal opioid-initiated cardioprotective effect via regulation of TRPV1 expression. Eur J Pharmacol. 2019; 844: 145-155. doi: 10.1016/j.ejphar.2018.12.007

36. van der Bijl P, Abou R, Goedemans L, Gersh BJ, Holmes DR Jr, Ajmone Marsan N, et al. Left ventricular post-infarct remodeling: Implications for systolic function improvement and outcomes in the modern era. JACC Heart Fail. 2020; 8(2): 131-140. doi: 10.1016/j.jchf.2019.08.014

37. Schuttler D, Clauss S, Weckbach LT, Brunner S. Molecular mechanisms of cardiac remodeling and regeneration in physical exercise. Cells. 2019; 8(10): 1128. doi: 10.3390/cells8101128

38. Smit M, Coetzee AR, Lochner A. The pathophysiology of myocardial ischemia and perioperative myocardial infarction. J Cardiothorac Vasc Anesth. 2020; 34(9): 2501-2512. doi: 10.1053/j.jvca.2019.10.00

39. Lin Y, Ding S, Chen Y, Xiang M, Xie Y. Cardiac adipose tissue contributes to cardiac repair: A review. Stem Cell Rev Rep. 2021; 17(4): 1137-1153. doi: 10.1007/s12015-020-10097-4

40. Revelo X, Parthiban P, Chen C, Barrow F, Fredrickson G, Wang H, et al. Cardiac resident macrophages prevent fibrosis and stimulate angiogenesis. Circ Res. 2021; 129(12): 1086-1101. doi: 10.1161/CIRCRESAHA.121.319737

41. Jenča D, Melenovský V, Stehlik J, Staněk V, Kettner J, Kautzner J, et al. Heart failure after myocardial infarction: Incidence and predictors. ESC Heart Fail. 2021; 8(1): 222-237. doi: 10.1002/ehf2.13144

42. Yu TS, Ge LZ, Cao JM. Research advances in sympathetic remodeling after myocardial infarction and its significance in forensic science. Fa Yi Xue Za Zhi. 2019; 35(1): 68-73. doi: 10.12116/j.issn.1004-5619.2019.01.013

43. Kosmas N, Manolis AS, Dagres N, Iliodromitis EK. Myocardial infarction or acute coronary syndrome with non-obstructive coronary arteries and sudden cardiac death: A missing connection. Europace. 2020; 22(9): 1303-1310. doi: 10.1093/europace/euaa156

44. Lyu J, Wang M, Kang X, Xu H, Cao Z, Yu T, et al. Macrophagemediated regulation of catecholamines in sympathetic neural remodeling after myocardial infarction. Basic Res Cardiol. 2020; 115(5): 56. doi: 10.1007/s00395-020-0813-3

45. Kytikova OY, Novgorodtseva TP, Antonyuk MV, Gvozdenko TA. The role of regulatory neuropeptides and neurotrophic factors in asthma pathophysiology. Russian Open Medical Journal. 2019; 8(4): e0402. doi: 10.15275/rusomj.2019.0402

46. Cuello AC. Levi-Montalcini R. NGF metabolism in health and in the Alzheimer’s pathology. Adv Exp Med Biol. 2021; 1331: 119-144. doi: 10.1007/978-3-030-74046-7_9

47. Paoletti F, Merzel F, Cassetta A, Ogris I, Covaceuszach S, Grdadolnik J, et al. Endogenous modulators of neurotrophin signaling: Landscape of the transient ATP-NGF interactions. Comput Struct Biotechnol J. 2021; 19: 2938-2949. doi: 10.1016/j.csbj.2021.05.009

48. Yamashita N. NGF signaling in endosomes. Adv Exp Med Biol. 2021; 1331: 19-29. doi: 10.1007/978-3-030-74046-7_3

49. Rowe CW, Dill T, Faulkner S, Gedye C, Paul JW, Tolosa JM, et al. The precursor for nerve growth factor (proNGF) in thyroid cancer lymph node metastases: Correlation with primary tumour and pathological variables. Int J Mol Sci. 2019; 20(5924). doi: 10.3390/ijms20235924

50. Kendall A, Nyström S, Ekman S, Hultén LM, Lindahl A, Hansson E, et al. Nerve growth factor in the equine joint. Vet J. 2021; 267: 105579. doi: 10.1016/j.tvjl.2020.105579

51. Liu Z, Wu H, Huang S. Role of NGF and its receptors in wound healing (Review). Exp Ther Med. 2021; 21(6): 599. doi: 10.3892/etm.2021.10031

52. Seidel MF, Lane NE. The evolution of nerve growth factor inhibition in clinical medicine. Nat Rev Rheumatol. 2021; 17(1): 34-46. doi: 10.1038/s41584-020-00528-4

53. Kang L, Andersen ND, Turek JW. Commentary: Connecting the dots: Coronary artery development as a combination of vasculogenesis and angiogenesis. J Thorac Cardiovasc Surg. 2021: S0022-5223(21)01224-1. doi: 10.1016/j.jtcvs.2021.08.026

54. Wu X, Reboll MR, Korf-Klingebiel M, Wollert KC. Angiogenesis after acute myocardial infarction. Cardiovasc Res. 2021; 117(5): 1257-1273. doi: 10.1093/cvr/cvaa287

55. Kurotsu S, Osakabe R, Isomi M, Tamura F, Sadahiro T, Muraoka N, et al. Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction. Biochem Biophys Res Commun. 2019; 495: 884-891. doi: 10.1016/j.bbrc.2017.11.094

56. Ferraro B, Leoni G, Hinkel R, Ormanns S, Paulin N, Ortega-Gomez A, et al. Pro-angiogenic macrophage phenotype to promote myocardial repair. J Am Coll Cardiol. 2019; 73: 2990-3002. doi: 10.1016/j.jacc.2019.03.503

57. Yang S, Cheng J, Man C, Jiang L, Long G, Zhao W, et al. Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury. J Orthop Surg Res. 2021; 16(1): 74. doi: 10.1186/s13018-021-02220-z

58. Julian K, Prichard B, Raco J, Jain R, Jain R. A review of cardiac autonomics: From pathophysiology to therapy. Future Cardiol. 2022; 18(2): 125-133. doi: 10.2217/fca-2021-0041

59. Kusayama T, Wan J, Yuan Y, Chen PS. Neural mechanisms and therapeutic opportunities for atrial fibrillation. Methodist Debakey Cardiovasc J. 2021; 17(1): 43-47. doi: 10.14797/FVDN2224

60. Shah R, Assis F, Alugubelli N, Okada DR, Cardoso R, Shivkumar K, et al. Cardiac sympathetic denervation for refractory ventricular arrhythmias in patients with structural heart disease: A systematic review. Heart Rhythm. 2019; 16(10): 1499-1505. doi: 10.1016/j.hrthm.2019.06.018

61. Aksu T, Gupta D, Pauza DH. Anatomy and physiology of intrinsic cardiac autonomic nervous system: Da Vinci anatomy card #2. JACC Case Rep. 2021; 3(4): 625-629. doi: 10.1016/j.jaccas.2021.02.018

62. Moss A, Robbins S, Achanta S, Kuttippurathu L, Turick S, Nieves S, et al. A single cell transcriptomics map of paracrine networks in the intrinsic cardiac nervous system. iScience. 2021; 24(7): 102713. doi: 10.1016/j.isci.2021.102713

63. Kusayama T, Wan J, Yuan Y, Chen PS. Neural mechanisms and therapeutic opportunities for atrial fibrillation. Methodist Debakey Cardiovasc J. 2021; 17(1): 43-47. doi: 10.14797/FVDN2224

64. Kotalczyk A, Mazurek M, Kalarus Z, Potpara TS, Lip GYH. Stroke prevention strategies in high-risk patients with atrial fibrillation. Nat Rev Cardiol. 2021; 18(4): 276-290. doi: 10.1038/s41569-020-00459-3

65. Sethwala AM, Goh I, Amerena JV. Combating inflammation in cardiovascular disease. Heart Lung Circ. 2021; 30(2): 197-206. doi: 10.1016/j.hlc.2020.09.003

66. Hutchings G, Kruszyna Ł, Nawrocki MJ, Strauss E, Bryl R, Spaczyńska J, et al. Molecular mechanisms associated with ROSdependent angiogenesis in lower extremity artery disease. Antioxidants (Basel). 2021; 10(5): 735. doi: 10.3390/antiox10050735

67. Bostan MM, Stătescu C, Anghel L, Șerban IL, Cojocaru E, Sascău R. Post-myocardial infarction ventricular remodeling biomarkers – The key link between pathophysiology and clinic. Biomolecules. 2020; 10(11): 1587. doi: 10.3390/biom10111587

68. Henning RJ. Cardiovascular exosomes and MicroRNAs in cardiovascular physiology and pathophysiology. J Cardiovasc Transl Res. 2021; 14(2): 195-212. doi: 10.1007/s12265-020-10040-5

69. Hu Y, Xiong J, Wen H, Wei H, Zeng X. MiR-98-5p promotes ischemia/reperfusion-induced microvascular dysfunction by targeting NGF and is a potential biomarker for microvascular reperfusion. Microcirculation. 2021; 28(1): e12657. doi: 10.1111/micc.12657

70. Zhao W, Zhao J, Rong J. Pharmacological modulation of cardiac remodeling after myocardial infarction. Oxid Med Cell Longev. 2020; 2020: 8815349. doi: 10.1155/2020/8815349

71. Pentz R, Iulita MF. The NGF metabolic pathway: New opportunities for biomarker research and drug target discovery: NGF pathway biomarkers and drug targets. Adv Exp Med Biol. 2021; 1331: 31-48. doi: 10.1007/978-3-030-74046-7_4

72. Gudasheva TA, Povarnina PY, Tarasiuk AV, Seredenin SB. Low-molecular mimetics of nerve growth factor and brain-derived neurotrophic factor: Design and pharmacological properties. Med Res Rev. 2020; 41(5): 2746-2774. doi: 10.1002/med.21721

73. Luo W, Gong Y, Qiu F, Yuan Y, Jia W, Liu Z, et al. NGF nanoparticles enhance the potency of transplanted human umbilical cord mesenchymal stem cells for myocardial repair. Am J Physiol Heart Circ Physiol. 2021; 320(5): H1959-H1974. doi: 10.1152/ajpheart.00855.2020

74. Saragovi HU, Galan A, Levin LA. Neuroprotection: Prosurvival and anti-neurotoxic mechanisms as therapeutic strategies in neurodegeneration. Front Cell Neurosci. 2019; 13: 231. doi: 10.3389/fncel.2019.00231

75. Dobbin SJH, Petrie MC, Myles RC, Touyz RM, Lang NN. Cardiotoxic effects of angiogenesis inhibitors. Clin Sci (Lond). 2021; 135(1): 71-100. doi: 10.1042/CS20200305