Статья
Инфламмасома - новый взгляд на терапию сердечно-сосудистых заболеваний: обзор. Часть I
В патогенезе многих воспалительных процессов важную роль играет каскад реакций различных видов инфламмасом. Продуктами их активации выступают провоспалительные цитокины интерлейкин (IL)-1β и IL-18. Эти белковые молекулы могут секретироваться двумя различными способами: везикулярным транспортом либо посредством образования пор в клеточной мембране, что в дальнейшем ведет к гибели секретирующей клетки. Роль активации инфламмасом в клетках сердечной ткани на настоящее время изучена недостаточно, однако есть некоторые исследования, отражающие связь запуска инфламмасомного каскада с развитием сердечно-сосудистых заболеваний. Таким образом, активация инфламмасом в кардиомиоцитах может приводить к электролитному дисбалансу, что впоследствии ведет к образованию эктопических очагов в сердечной ткани и нарушению сердечного ритма. Запуск инфламмасомного каскада в сердечных фибробластах способствует формированию фиброза и ремоделированию ткани миокарда, что приводит к нарушению функциональной активности сердца. Активация инфламмасомы в эндотелиоцитах коронарных артерий приводит к эндотелиальной дисфункции и атерогенезу. Таким образом, активация различных видов инфламмасом в сердечной ткани приводит к формированию сердечной патологии.
1. Zheng D, Liwinski T, Elinav E. Inflammasome activation and regulation: toward a better understanding of complex mechanisms. Cell Discov. 2020;6:36. doi:10.1038/s41421-020-0167-x.
2. Kelley N, Jeltema D, Duan Y, et al. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int J Mol Sci. 2019;20(13):3328. doi:10.3390/ijms20133328.
3. Strowig T, Henao-Mejia J, Elinav E, et al. Inflammasomes in health and disease. Nature. 2012;481(7381):278-86. doi:10.1038/nature10759.
4. Ting JPY, Lovering RC, Alnemri ES, et al. The NLR gene family: a standard nomenclature. Immunity. 2008;28(3):285-7. doi:10.1016/j.immuni.2008.02.005.
5. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229-65. doi:10.1146/annurev.immunol.021908.132715.
6. Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021;6(1):291. doi:10.1038/s41392-021-00687-0.
7. Liu Z, Chen Y, Mei Y, et al. Gasdermin D-Mediated Pyroptosis in Diabetic Cardiomyopathy: Molecular Mechanisms and Pharmacological Implications. Molecules. 2023;28(23): 7813. doi:10.3390/molecules28237813.
8. Bracey NA, Gershkovich B, Chun J, et al. Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome. J Biol Chem. 2014;289(28):19571-84. doi:10.1074/jbc.M114.550624.
9. Bai B, Yang Y, Wang Q, et al. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis. 2020;11(9):776. doi:10.1038/s41419-020-02985-x.
10. Bryan NB, Dorfleutner A, Kramer SJ, et al. Differential splicing of the apoptosisassociated speck like protein containing a caspase recruitment domain (ASC) regulates inflammasomes. J Inflamm Lond Engl. 2010;7:23. doi:10.1186/1476-9255-7-23.
11. Li Y, Fu TM, Lu A, et al. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc Natl Acad Sci U S A. 2018;115(43):10845-52. doi:10.1073/pnas.1810524115.
12. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5(4):a008656. doi:10.1101/cshperspect.a008656.
13. Lu A, Magupalli VG, Ruan J, et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell. 2014;156(6):1193-206. doi:10.1016/j.cell.2014.02.008.
14. Van Opdenbosch N, Lamkanfi M. Caspases in Cell Death, Inflammation, and Disease. Immunity. 2019;50(6):1352-64. doi:10.1016/j.immuni.2019.05.020.
15. Hornung V, Latz E. Critical functions of priming and lysosomal damage for NLRP3 activation. Eur J Immunol. 2010;40(3):620-3. doi:10.1002/eji.200940185.
16. Lee DJ, Du F, Chen SW, et al. Regulation and function of the caspase-1 in an inflammatory microenvironment. J Invest Dermatol. 2015;135(8):2012. doi:10.1038/jid.2015.119.
17. Dai Y, Zhou J, Shi C. Inflammasome: structure, biological functions, and therapeutic targets. MedComm. 2023;4(5):e391. doi:10.1002/mco2.391.
18. Tang T, Gong T, Jiang W, et al. GPCRs in NLRP3 Inflammasome Activation, Regulation, and Therapeutics. Trends Pharmacol Sci. 2018;39(9):798-811. doi:10.1016/j.tips.2018.07.002.
19. He Y, Zeng MY, Yang D, et al. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature. 2016;530(7590):354-7. doi:10.1038/nature16959.
20. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002; 10(2):417-26. doi:10.1016/s1097-2765(02)00599-3.
21. He W ting, Wan H, Hu L, et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 2015;25(12):1285-98. doi:10.1038/cr.2015.139.
22. Zhang M, Kenny SJ, Ge L, et al. Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion. eLife. 4:e11205. doi:10.7554/eLife.11205.
23. Gaidt MM, Ebert TS, Chauhan D, et al. Human Monocytes Engage an Alternative Inflammasome Pathway. Immunity. 2016;44(4):833-46. doi:10.1016/j.immuni.2016.01.012.
24. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519-50. doi:10.1146/annurev.immunol.021908.132612.
25. Sahoo M, Ceballos-Olvera I, del Barrio L, et al. Role of the Inflammasome, IL-1β, and IL-18 in Bacterial Infections. Sci World J. 2011;11:2037-50. doi:10.1100/2011/212680.
26. Chen G, Chelu MG, Dobrev D, et al. Cardiomyocyte Inflammasome Signaling in Cardiomyopathies and Atrial Fibrillation: Mechanisms and Potential Therapeutic Implications. Front Physiol. 2018;9:1115. doi:10.3389/fphys.2018.01115.
27. Pomerantz BJ, Reznikov LL, Harken AH, et al. Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1β. Proc Natl Acad Sci U S A. 2001;98(5):2871-6. doi:10.1073/pnas.041611398.
28. Toldo S, Mauro AG, Cutter Z, et al. Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury. Am J Physiol - Heart Circ Physiol. 2018;315(6):H1553- H1568. doi:10.1152/ajpheart.00158.2018.
29. Bauernfeind FG, Horvath G, Stutz A, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol Baltim Md 1950. 2009;183(2):787-91. doi:10.4049/jimmunol.0901363.
30. Liao Y, Liu K, Zhu L. Emerging Roles of Inflammasomes in Cardiovascular Diseases. Front Immunol. 2022;13:834289. doi:10.3389/fimmu.2022.834289.
31. Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol Pharm Bull. 2005;28(5):886-92. doi:10.1248/bpb.28.886.
32. Yu L, Feng Z. The Role of Toll-Like Receptor Signaling in the Progression of Heart Failure. Mediators Inflamm. 2018;2018:9874109. doi:10.1155/2018/9874109.
33. Xu H, Yu W, Sun S, et al. TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3- dependent manner. Sci Bull. 2021;66(16):1669-83. doi:10.1016/j.scib.2021.01.030.
34. Akosile W, Voisey J, Lawford B, et al. The inflammasome NLRP12 is associated with both depression and coronary artery disease in Vietnam veterans. Psychiatry Res. 2018;270: 775-9. doi:10.1016/j.psychres.2018.10.051.
35. Johansson Å, Eriksson N, Becker RC, et al. NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes: GenomeWide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO). Circ Cardiovasc Genet. 2015;8(3):498-506. doi:10.1161/CIRCGENETICS.114.000724.
36. Onódi Z, Ruppert M, Kucsera D, et al. AIM2-driven inflammasome activation in heart failure. Cardiovasc Res. 2021;117(13):2639-51. doi:10.1093/cvr/cvab202.
37. Wang P, Zhang W, Feng Z, et al. LDL-induced NLRC3 inflammasome activation in cardiac fibroblasts contributes to cardiomyocytic dysfunction. Mol Med Rep. 2021;24(1):526. doi:10.3892/mmr.2021.12165.
38. Shi H, Gao Y, Dong Z, et al. GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury. Circ Res. 2021;129(3):383-96. doi:10.1161/CIRCRESAHA.120.318629.
39. Artlett CM. The Mechanism and Regulation of the NLRP3 Inflammasome during Fibrosis. Biomolecules. 2022;12(5):634. doi:10.3390/biom12050634.
40. Artlett CM, Sassi-Gaha S, Rieger JL, et al. The inflammasome activating caspase 1 mediates fibrosis and myofibroblast differentiation in systemic sclerosis. Arthritis Rheum. 2011;63(11):3563-74. doi:10.1002/art.30568.
41. Artlett CM, Sassi-Gaha S, Hope JL, et al. Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis. Arthritis Res Ther. 2017;19(1):144. doi:10.1186/s13075-017-1331-z.
42. Yao C, Veleva T, Scott L, et al. Enhanced Cardiomyocyte NLRP3 Inflammasome Signaling Promotes Atrial Fibrillation. Circulation. 2018;138(20):2227-42. doi:10.1161/CIRCULATIONAHA.118.035202.
43. Heijman J, Muna AP, Veleva T, et al. Atrial Myocyte NLRP3/CaMKII Nexus Forms a Substrate for Postoperative Atrial Fibrillation. Circ Res. 2020;127(8):1036-55. doi:10.1161/CIRCRESAHA.120.316710.
44. Denham NC, Pearman CM, Caldwell JL, et al. Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure. Front Physiol. 2018;9:1380. doi:10.3389/fphys.2018.01380.
45. Gawałko M, Saljic A, Li N, et al. Adiposity-associated atrial fibrillation: molecular determinants, mechanisms, and clinical significance. Cardiovasc Res. 2023;119(3):614-30. doi:10.1093/cvr/cvac093.
46. Scott Jr L, Fender AC, Saljic A, et al. NLRP3 inflammasome is a key driver of obesityinduced atrial arrhythmias. Cardiovasc Res. 2021;117(7):1746-59. doi:10.1093/cvr/cvab024.
47. Li P, Kurata Y, Taufiq F, et al. Kv1.5 channel mediates monosodium urate-induced activation of NLRP3 inflammasome in macrophages and arrhythmogenic effects of urate on cardiomyocytes. Mol Biol Rep. 2022;49(7):5939-52. doi:10.1007/s11033-022-07378-1.
48. Galea J, Armstrong J, Gadsdon P, et al. Interleukin-1 beta in coronary arteries of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol. 1996;16(8):1000-6. doi:10.1161/01.atv.16.8.1000.
49. Zheng F, Gong Z, Xing S, et al. Overexpression of caspase-1 in aorta of patients with coronary atherosclerosis. Heart Lung Circ. 2014;23(11):1070-4. doi:10.1016/j.hlc.2014.04.256.
50. Gaul S, Schaeffer KM, Opitz L, et al. Extracellular NLRP3 inflammasome particles are internalized by human coronary artery smooth muscle cells and induce pro-atherogenic effects. Sci Rep. 2021;11(1):15156. doi:10.1038/s41598-021-94314-1.