Статья
Клеточная гетерогенность и клональный гемопоэз клеток иммунной системы при атеросклерозе
Недавние исследования в области секвенирования РНК единичных клеток улучшили понимание структуры субпопуляции иммунных клеток при атеросклерозе. С помощью новых технологий выявлены новые субпопуляции иммунных клеток, участвующих в атеросклерозе. Кроме того, появился относительно распространенный и сильный фактор сердечно-сосудистого риска: клональный гемопоэз с неопределенным потенциалом, возникающий в результате накопления соматических мутаций в течение жизни с формированием популяций мутантных клонов циркулирующих лейкоцитов. Лица с таким состоянием имеют высокий риск сердечно-сосудистых осложнений, таких как инфаркт миокарда и инсульт, вне зависимости от традиционных факторов риска. В данном обзоре освещаются последние данные в области исследования клеточной гетерогенности клеток иммунной системы при атеросклерозе, а также роль клонального гемопоэза в его развитии.
1. Libby P, Hansson GK. From Focal Lipid Storage to Systemic Inflammation: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;74:1594-607. doi:10.1016/j.jacc.2019.07.061.
2. Hansen SEJ, Madsen CM, Varbo A, et al. Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population. Clin Chem. 2019;65:321- 32. doi:10.1373/clinchem.2018.294926.
3. Xiao L, Harrison DG. Inflammation in Hypertension. Can J Cardiol. 2020;36:635-47. doi:10.1016/j.cjca.2020.01.013.
4. Ridker PM. A Test in Context: High-Sensitivity C-Reactive Protein. J Am Coll Cardiol. 2016;67:712-23. doi:10.1016/j.jacc.2015.11.037.
5. Ketelhuth DF, Hansson GK. Adaptive Response of T and B Cells in Atherosclerosis. Circ Res. 2016;118:668-78. doi:10.1161/CIRCRESAHA.115.306427.
6. Hansson GK. Inflammation and Atherosclerosis: The End of a Controversy. Circulation. 2017;136:1875-7. doi:10.1161/CIRCRESAHA.118.313591.
7. Baylis RA, Gomez D, Mallat Z, et al. The CANTOS Trial: One Important Step for Clinical Cardiology but a Giant Leap for Vascular Biology. Arterioscler Thromb Vasc Biol. 2017;37:e174-e177. doi:10.1161/ATVBAHA.117.310097
8. Hansson E. Primary astroglial cultures. A biochemical and functional evaluation. Neurochem Res. 1986;11:759-67. doi:10.1007/BF00965202.
9. Tang J, van PN, Kastenmüller W, Germain RN. The future of immunoimaging–deeper, bigger, more precise, and definitively more colorful. Eur J Immunol. 2013;43:1407-12. doi:10.1002/eji.201243119.
10. Galkina E, Kadl A, Sanders J, et al. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med. 2006;203:1273-82. doi:10.1084/jem.20052205.
11. Cole JE, Park I, Ahern DJ, et al. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity. Cardiovasc Res. 2018;114:1360- 71. doi:10.1093/cvr/cvy109.
12. Winkels H, Ehinger E, Vassallo M, et al. Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry. Circ Res. 2018;122:1675-88. doi:10.1161/CIRCRESAHA.117.312513.
13. Robbins CS, Hilgendorf I, Weber GF, et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med. 2013;19:1166-72. doi:10.1038/nm.3258.
14. Yurdagul AJ, Doran AC, Cai B, et al. Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis. Front Cardiovasc Med. 2017;4:86. doi:10.3389/fcvm.2017.00086.
15. Lichtman AH, Binder CJ, Tsimikas S, et al. Adaptive immunity in atherogenesis: new insights and therapeutic approaches. J Clin Invest. 2013;123:27-36. doi:10.1172/JCI63108.
16. Gisterå A, Hansson GK. The immunology of atherosclerosis. Nat Rev Nephrol. 2017;13:368- 80. doi:10.1038/nrneph.2017.51.
17. Swirski FK, Libby P, Aikawa E, et al. Ly-6Chi monocytes dominate hypercholesterolemiaassociated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007;117:195-205. doi:10.1172/JCI29950.
18. Tacke F, Alvarez D, Kaplan TJ, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest. 2007;117:185-94. doi:10.1172/JCI28549.
19. Bennett MR, Sinha S, Owens GK. Vascular Smooth Muscle Cells in Atherosclerosis. Circ Res. 2016;118:692-702. doi:10.1161/CIRCRESAHA.115.306361.
20. Kubo T, Maehara A, Mintz GS, et al. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J Am Coll Cardiol. 2010;55:1590-7. doi:10.1016/j.jacc.2009.07.078.
21. Deliargyris EN. Intravascular ultrasound virtual histology derived thin cap fibroatheroma now you see it, now you don’t. J Am Coll Cardiol. 2010;55:1598-9. doi:10.1016/j.jacc.2009.10.069.
22. Vergallo R, Crea F. Atherosclerotic Plaque Healing. N Engl J Med. 2020;383:846-57. doi:10.1056/NEJMra2000317.
23. Williams JW, Winkels H, Durant CP, et al. Single Cell RNA Sequencing in Atherosclerosis Research. Circ Res. 2020;126:1112-26. doi:10.1161/CIRCRESAHA.119.315940.
24. Kalluri AS, Vellarikkal SK, Edelman ER, et al. Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations. Circulation. 2019;140:147-63. doi:10.1161/CIRCULATIONAHA.118.038362.
25. Kalucka J, de Rooij LPMH, Goveia J, et al. Single-Cell Transcriptome Atlas of Murine Endothelial Cells. Cell. 2020;180:764-79.e20. doi:10.1016/j.cell.2020.01.015.
26. Fernandez DM, Rahman AH, Fernandez NF, et al. Single-cell immune landscape of human atherosclerotic plaques. Nat Med. 2019;25:1576-88. doi:10.1038/s41591-019-0590-4.
27. Wirka RC, Wagh D, Paik DT, et al. Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. Nat Med. 2019;25:1280-9. doi:10.1038/s41591-019-0512-5.
28. Depuydt MAC, Prange KHM, Slenders L, et al. Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics. Circ Res. 2020;127:1437-55. doi:10.1161/CIRCRESAHA.120.316770.
29. Kovalcsik E, Antunes RF, Baruah P, et al. Proteasome-mediated reduction in proapoptotic molecule Bim renders CD4+CD28null T cells resistant to apoptosis in acute coronary syndrome. Circulation. 2015;131:709-20. doi:10.1161/CIRCULATIONAHA.114.013710.
30. Liuzzo G, Goronzy JJ, Yang H, et al. Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation. 2000;101:2883-8. doi:10.1161/01.cir.101.25.2883.
31. Téo FH, de ORT, Mamoni RL, et al. Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis. Cell Immunol. 2013;281:11-9. doi:10.1016/j.cellimm.2013.01.007.
32. Horiuchi T, Hirokawa M, Kawabata Y, et al. Identification of the T cell clones expanding within both CD8(+)CD28(+) and CD8(+)CD28(-) T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire. Bone Marrow Transplant. 2001;27:731-9. doi:10.1038/sj.bmt.1702859.
33. Scheuring UJ, Sabzevari H, Theofilopoulos AN. Proliferative arrest and cell cycle regulation in CD8(+)CD28(-) versus CD8(+)CD28(+) T cells. Hum Immunol. 2002;63:1000-9. doi:10.1016/s0198-8859(02)00683-3.
34. Martín P, Blanco-Domínguez R, Sánchez-Díaz R. Novel human immunomodulatory T cell receptors and their double-edged potential in autoimmunity, cardiovascular disease and cancer. Cell Mol Immunol. 2021;18:919-35. doi:10.1038/s41423-020-00586-4.
35. Sancho D, Gómez M, Sánchez-Madrid F. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol. 2005;26:136-40. doi:10.1016/j.it.2004.12.006.
36. Cremer S, Michalik KM, Fischer A, et al. Hematopoietic Deficiency of the Long Noncoding RNA MALAT1 Promotes Atherosclerosis and Plaque Inflammation. Circulation. 2019;139:1320-34. doi:10.1161/CIRCULATIONAHA.117.029015.
37. Zhao M, Wang S, Li Q, et al. MALAT1: A long non-coding RNA highly associated with human cancers. Oncol Lett. 2018;16:19-26. doi:10.3892/ol.2018.8613.
38. Liu J, Peng WX, Mo YY, et al. MALAT1-mediated tumorigenesis. Front Biosci (Landmark Ed). 2017;22:66-80. doi:10.2741/4472.
39. Zhang B, Arun G, Mao YS, et al. The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep. 2012;2:111-23. doi:10.1016/j.celrep.2012.06.003.
40. Burel JG, Pomaznoy M, Lindestam ACS, et al. Circulating T cell-monocyte complexes are markers of immune perturbations. Elife. 2019;8: doi:10.7554/eLife.46045.
41. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371:2488-98. doi:10.1056/NEJMoa1408617.
42. Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371:2477-87. doi:10.1056/NEJMoa1409405.
43. Busque L, Buscarlet M, Mollica L, et al. Concise Review: Age-Related Clonal Hematopoiesis: Stem Cells Tempting the Devil. Stem Cells. 2018;36:1287-94. doi:10.1002/stem.2845.
44. Jaiswal S, Natarajan P, Silver AJ, et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017;377:111-21. doi:10.1056/NEJMoa1701719.
45. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126:9-16. doi:10.1182/blood-2015-03-631747.
46. 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;74:567-77. doi:10.1016/j.jacc.2019.06.007.
47. Schloss MJ, Swirski FK, Nahrendorf M. Modifiable Cardiovascular Risk, Hematopoiesis, and Innate Immunity. Circ Res. 2020;126:1242-59. doi:10.1161/CIRCRESAHA.120.315936.
48. Libby P, Nahrendorf M, Swirski FK. Leukocytes Link Local and Systemic Inflammation in Ischemic Cardiovascular Disease: An Expanded Cardiovascular Continuum. J Am Coll Cardiol. 2016;67:1091-103. doi:10.1016/j.jacc.2015.12.048.
49. Fuster JJ, MacLauchlan S, Zuriaga MA, et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355:842-7. doi:10.1126/science.aag1381.
50. Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559:400-4. doi:10.1038/s41586-018-0317-6.
51. Desai P, Mencia-Trinchant N, Savenkov O, et al. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nat Med. 2018;24:1015-23. doi:10.1038/s41591-018-0081-z.
52. Sellar RS, Jaiswal S, Ebert BL. Predicting progression to AML. Nat Med. 2018;24:904-6. doi:10.1038/s41591-018-0114-7.
53. 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;4:25-33. doi:10.1001/jamacardio.2018.3965.
54. Libby P, Jaiswal S, Lin AE, et al. CHIPping Away at the Pathogenesis of Heart Failure. JAMA Cardiol. 2019;4:5-6. doi:10.1001/jamacardio.2018.4039.