Статья
Клональный гемопоэз неопределённого потенциала и хроническая сердечная недостаточность
Современные исследования демонстрируют, что клональный гемопоэз неопределенного потенциала (КГНП) является фактором риска развития и прогноза хронической сердечной недостаточности (ХСН) различной этиологии. Патофизиология и последствия КГНП носят геноспецифичный характер. Механизмы, задействованные в этом процессе, сложны и указывают на центральную роль системного и миокардиального воспаления, включая иммунный ответ, зависящий от каскада инфламмасома/интерлейкин-1β/интерлейкин-6. КГНП и ассоциируемые с ним воспалительные пути представляют собой мощную потенциальную мишень, что обусловливает актуальность научных работ в зоне различных стадий ХСН и маркеров этого генетического феномена. Лучшее понимание взаимодействий между мутантными клонами, иммунными путями, хроническим воспалением и клинической реализацией ХСН может иметь важное значение в контексте прецизионной и персонализированной медицины.
1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/ American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063.
2. Murphy SP, Kakkar R, McCarthy CP, et al. Inflammation in Heart Failure: JACC State-ofthe-Art Review. J Am Coll Cardiol. 2020;75(11):1324-40. doi:10.1016/j.jacc.2020.01.014.
3. Rauchhaus M, Doehner W, Francis DP, et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation. 2000;102(25):3060-7. doi:10.1161/01.cir.102.25.3060.
4. Florez MA, Tran BT, Wathan TK, et al. Clonal hematopoiesis: Mutation-specific adaptation to environmental change. Cell Stem Cell. 2022;29(6):882-904. doi:10.1016/j.stem.2022.05.006.
5. Haring B, Wissel S, Manson JE. Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk. Curr Cardiol Rep. 2022;24(8):1049-58. doi:10.1007/s11886-022-01724-2.
6. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9-16. doi:10.1182/blood-2015-03-631747.
7. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488-98. doi:10.1056/NEJMoa1408617.
8. Jaiswal S, Natarajan P, Silver AJ, et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017;377(2):111-21. doi:10.1056/NEJMoa1701719.
9. Mas-Peiro S, Hoffmann J, Fichtlscherer S, et al. Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation. Eur Heart J. 2020;41(8):933-9. doi:10.1093/eurheartj/ehz591.
10. Wolach O, Sellar RS, Martinod K, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci Transl Med. 2018; 10(436):eaan8292. doi:10.1126/scitranslmed.aan8292.
11. Kimishima Y, Misaka T, Yokokawa T, et al. Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils. Nat Commun. 2021;12(1):6177. doi:10.1038/s41467-021-26435-0.
12. Jensen JL, Easaw S, Anderson T, et al. Clonal Hematopoiesis and the Heart: a Toxic Relationship. Curr Oncol Rep. 2023;25(5):455-63. doi:10.1007/s11912-023-01398-1.
13. Слепцов А.А., Назаренко М. С., Пузырев В. П. Общее в атеро и канцерогенезе: клональный гемопоэз. Российский кардиологический журнал. 2023;28(10):5511. doi:10.15829/1560-4071-2023-5511.
14. Bick AG, Pirruccello JP, Griffin GK, et al. Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis. Circulation. 2020;141(2):124-31. doi:10.1161/CIRCULATIONAHA.119.044362.
15. Mayerhofer E, Strecker C, Becker H, et al. Prevalence and Therapeutic Implications of Clonal Hematopoiesis of Indeterminate Potential in Young Patients With Stroke. Stroke. 2023;54(4):938-46. doi:10.1161/STROKEAHA.122.041416.
16. Bick AG, Weinstock JS, Nandakumar SK, et al. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature. 2020;586(7831):763-8. doi:10.1038/s41586-020-2819-2.
17. Sikking MA, Stroeks SLVM, Waring OJ, et al. Clonal Hematopoiesis of Indeterminate Potential From a Heart Failure Specialist's Point of View. J Am Heart Assoc. 2023;12 (15):e030603. doi:10.1161/JAHA.123.030603.
18. Stacey SN, Zink F, Halldorsson GH, et al. Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis. Nat Genet. 2023;55(12):2149-59. doi:10.1038/s41588-023-01555-z.
19. Kandarakov O, Belyavsky A. Clonal Hematopoiesis, Cardiovascular Diseases and Hematopoietic Stem Cells. Int J Mol Sci. 2020;21(21):7902. doi:10.3390/ijms21217902.
20. Challen GA, Goodell MA. Clonal hematopoiesis: mechanisms driving dominance of stem cell clones. Blood. 2020;136(14):1590-8. doi:10.1182/blood.2020006510.
21. Avagyan S, Henninger JE, Mannherz WP, et al. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. Science. 2021;374(6568):768-72. doi:10.1126/science.aba9304.
22. Zhang Q, Zhao K, Shen Q, et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature. 2015;525:389-93. doi:10.1038/nature15252.
23. Sano S, Oshima K, Wang Y, et al. Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1β/NLRP3 Inflammasome. J Am Coll Cardiol. 2018;71(8):875-86. doi:10.1016/j.jacc.2017.12.037.
24. Abplanalp WT, Cremer S, John D, et al. Clonal Hematopoiesis-Driver DNMT3A Mutations Alter Immune Cells in Heart Failure. Circ Res. 2021;128(2):216-28. doi:10.1161/ CIRCRESAHA.120.317104.
25. Sano S, Oshima K, Wang Y, et al. CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease. Circ Res. 2018;123(3):335-41. doi:10.1161/CIRCRESAHA.118.313225.
26. Sano S, Wang Y, Yura Y, et al. JAK2V617F-Mediated Clonal Hematopoiesis Accelerates Pathological Remodeling in Murine Heart Failure. JACC Basic Transl Sci. 2019;4(6): 684-97. doi:10.1016/j.jacbts.2019.05.013.
27. Fidler TP, Xue C, Yalcinkaya M, et al. The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. Nature. 2021;592(7853):296-301. doi:10.1038/s41586-021-03341-5.
28. Jaiswal S, Libby P.Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease. Nat Rev Cardiol. 2020;17(3):137-44. doi:10.1038/s41569-019-0247-5.
29. Jaiswal S. Clonal hematopoiesis and nonhematologic disorders. Blood. 2020;136(14): 1606-14. doi:10.1182/blood.2019000989.
30. Wang W, Liu W, Fidler T, et al. Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2 V617F Mice. Circulation Research. 2018;123:e35- e47. doi:10.1161/circresaha.118.313283.
31. Abplanalp WT, Mas-Peiro S, Cremer S, et al. Association of clonal hematopoiesis of indeterminate potential with inflammatory gene expression in patients with severe degenerative aortic valve stenosis or chronic postischemic heart failure. JAMA Cardiol. 2020;5:1170-5. doi:10.1001/jamacardio.2020.2468.
32. Sano S, Wang Y, Ogawa H, et al. TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophilmediated cytotoxic response. JCI Insight. 2021 Jul 8;6(13):e146076. doi:10.1172/jci.insight.146076.
33. Yura Y, Miura-Yura E, Katanasaka Y, et al. The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Ppm1d Promotes Inflammation and Non-Ischemic Heart Failure in Mice. Circ Res. 2021;129(6):684-98. doi:10.1161/CIRCRESAHA.121.319314.
34. Liao M, Chen R, Yang Y, et al. Aging-elevated inflammation promotes DNMT3A R878Hdriven clonal hematopoiesis. Acta Pharm Sin B. 2022;12:678-91. doi:10.1016/j.apsb.2021.09.015.
35. Abegunde SO, Buckstein R, Wells RA, et al. An inflammatory environment containing TNFα favors Tet2-mutant clonal hematopoiesis. Exp Hematol. 2018;59:60-5. doi: 10.1016/j.exphem.2017.11.002.
36. Yura Y, Sano S, Walsh K. Clonal Hematopoiesis: A New Step Linking Inflammation to Heart Failure. JACC Basic Transl Sci. 2020;5(2):196-207. doi:10.1016/j.jacbts.2019.08.006.
37. Abplanalp WT, Schuhmacher B, Cremer S, et al. Cell-intrinsic effects of clonal hematopoiesis in heart failure. Nat Cardiovasc Res. 2023;2:819-34. doi:10.1038/s44161-023-00322-x.
38. Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science. 2019;366(6465):eaan4673. doi:10.1126/science.aan4673.
39. Piepoli MF, Adamo M, Barison A, et al. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2022;29(1):275-300. doi:10.1093/eurjpc/zwab147.
40. Van Deuren RC, Andersson-Assarsson JC, Kristensson FM, et al. Expansion of mutationdriven haematopoietic clones is associated with insulin resistance and low HDL-cholesterol in individuals with obesity. bioRxiv, 2021.05.12.443095. doi:10.1101/2021.05.12.443095.
41. Miller PG, Qiao D, Rojas-Quintero J, et al. Association of clonal hematopoiesis with chronic obstructive pulmonary disease. Blood. 2022;139(3):357-68. doi:10.1182/blood.2021013531.
42. Vlasschaert C, McNaughton AJM, Chong M, et al. Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease. J Am Soc Nephrol. 2022;33(5):985-95. doi:10.1681/ASN.2021060774.
43. Komic L, Kumric M, Urlic H, et al. Obesity and Clonal Hematopoiesis of Indeterminate Potential: Allies in Cardiovascular Diseases and Malignancies. Life (Basel). 2023;13(6):1365. doi:10.3390/life13061365.
44. Hatakeyama K, Hieda M, Semba Y, et al. TET2 Clonal Hematopoiesis Is Associated With Anthracycline-Induced Cardiotoxicity in Patients With Lymphoma. JACC CardioOncol. 2022;4(1):141-3. doi:10.1016/j.jaccao.2022.01.098.
45. Yu B, Roberts MB, Raffield LM, et al. National Heart, Lung, and Blood Institute TOP Med Consortium. Supplemental Association of Clonal Hematopoiesis with Incident Heart Failure. J Am Coll Cardiol. 2021;78(1):42-52. doi:10.1016/j.jacc.2021.04.085.
46. Shi C, Aboumsallem JP, Suthahar N, et al. Clonal hematopoiesis of indeterminate potential: associations with heart failure incidence, clinical parameters and biomarkers. Eur J Heart Fail. 2023;25(1):4-13. doi:10.1002/ejhf.2715.
47. Scolari FL, Abelson S, Brahmbhatt DH, et al. Clonal haematopoiesis is associated with higher mortality in patients with cardiogenic shock. Eur J Heart Fail. 2022;24(9):1573-82. doi:10.1002/ejhf.2588.
48. Dorsheimer L, Assmus B, Rasper T, et al. Association of Mutations Contributing to Clonal Hematopoiesis With Prognosis in Chronic Ischemic Heart Failure. JAMA Cardiol. 2019; 4(1):25-33. doi:10.1001/jamacardio.2018.3965.
49. Assmus B, Cremer S, Kirschbaum K, et al. Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations. Eur Heart J. 2021;42(3):257-65. doi:10.1093/eurheartj/ehaa845.
50. Kiefer KC, Cremer S, Pardali E, et al. Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality. ESC Heart Fail. 2021;8(3):1873-84. doi:10.1002/ehf2.13297.
51. Pascual-Figal DA, Bayes-Genis A, Díez-Díez M, et al. Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction. J Am Coll Cardiol. 2021;77(14):1747-59. doi:10.1016/j.jacc.2021.02.028.
52. Cremer S, Kirschbaum K, Berkowitsch A, et al. Multiple Somatic Mutations for Clonal Hematopoiesis Are Associated With Increased Mortality in Patients With Chronic Heart Failure. Circ Genom Precis Med. 2020;13(4):e003003. doi:10.1161/CIRCGEN.120.003003.
53. Palomo L, Santiago-Vacas E, Pascual-Figal D, et al. Prevalence and characteristics of clonal hematopoiesis in heart failure. Rev Esp Cardiol (Engl Ed). 2021;74(11):996-9. English, Spanish. doi:10.1016/j.rec.2021.05.005.
54. Pugliese NR, Pellicori P, Filidei F, et al. Inflammatory pathways in heart failure with preserved left ventricular ejection fraction: implications for future interventions. Cardiovasc Res. 2023;118(18):3536-55. doi:10.1093/cvr/cvac133.
55. Cochran JD, Yura Y, Thel MC, et al. Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction. Circulation. 2023;148(15):1165-78. doi:10.1161/CIRCULATIONAHA.123.064170.
56. Svensson EC, Madar A, Campbell CD, et al. TET2-Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial. JAMA Cardiol. 2022;7(5):521-8. doi:10.1001/jamacardio.2022.0386.
57. Tall AR, Fuster JJ. Clonal hematopoiesis in cardiovascular disease and therapeutic implications. Nat Cardiovasc Res. 2022;1(2):116-24. doi:10.1038/s44161-021-00015-3.
58. Zuriaga MA, Pascual-Figal D, Fuster JJ. Clonal haematopoiesis and cardiac arrythmias: rhythm-altering mutations. Eur Heart J. 2024;45(10):806-8. doi:10.1093/eurheartj/ehae052.
59. Ahn HJ, An HY, Ryu G, et al. Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study. Eur Heart J. 2024;45(10):778-90. doi:10.1093/eurheartj/ehad869.
60. Schuermans A, Vlasschaert C, Nauffal V, et al. Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias. Eur Heart J. 2024;45(10):791-805. doi:10.1093/eurheartj/ehad670.
61. Libby P, Sidlow R, Lin AE, et al. Clonal Hematopoiesis: Crossroads of Aging, Cardiovascular Disease, and Cancer: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;74(4):567-77. doi:10.1016/j.jacc.2019.06.007.
62. de Boer RA, Hulot JS, Tocchetti CG, et al. Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020;22(12):2272-89. doi:10.1002/ejhf.2029.
63. Aboumsallem JP, Moslehi J, de Boer RA. Reverse Cardio-Oncology: Cancer Development in Patients With Cardiovascular Disease. J Am Heart Assoc. 2020;9(2):e013754. doi:10.1161/JAHA.119.013754.
64. Kadowaki H, Akazawa H, Shindo A, et al. Shared and Reciprocal Mechanisms Between Heart Failure and Cancer - An Emerging Concept of Heart-Cancer Axis. Circ J. 2024; 88(2):182-8. doi:10.1253/circj.CJ-23-0838.
65. Stein A, Metzeler K, Kubasch AS, et al. Clonal hematopoiesis and cardiovascular disease: deciphering interconnections. Basic Res Cardiol. 2022;117(1):55. doi:10.1007/s00395-022-00969-w.
66. Шляхто Е.В., Беленков Ю.Н., Бойцов С.А. и др. Результаты промежуточного анализа проспективного наблюдательного многоцентрового регистрового исследования пациентов с хронической сердечной недостаточностью в Российской Федерации "ПРИОРИТЕТХСН": исходные характеристики и лечение первых включенных пациентов. Российский кардиологический журнал. 2023;28(10):5593. doi:10.15829/1560-4071-2023-5593.