Статья
Инфламмасома — новый взгляд на терапию сердечно-сосудистых заболеваний. Часть II
Роль инфламмасом при сердечно-сосудистых заболеваниях в настоящее время изучена недостаточно, однако есть некоторое количество исследований последних лет, показывающих участие этих мультибелковых комплексов в развитии и прогрессировании сердечно-сосудистых заболеваний. Так, при фибрилляции предсердий запуск инфламмасомы способствует уменьшению длительности и рефрактерности предсердного потенциала действия, индукции ранней и/или отсроченной постдеполяризации, что поддерживает эктопическую активность. При хронической сердечной недостаточности запуск инфламмасомного каскада инициирует и поддерживает хроническое воспаление, приводящее к ремоделированию сердечной ткани и развитию фиброза. В ишемической болезни сердца активация инфламмасомы способствует поддержанию ишемии и увеличению области очагов некроза. Воспалительные реакции при перикардитах и миокардитах также не обходятся без участия этого мультибелкового комплекса. При данных патологиях ингибирование инфламмасомы способствует улучшению клинической симптоматики и нормализации функциональной способности сердечной ткани. Таким образом, при вышеперечисленных заболеваниях использование препаратов-ингибиторов инфламмасом может стать достаточно перспективным методом терапии.
1. 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.
2. Li L, Coarfa C, Yuan Y, et al. Fibroblast-specific inflammasome activation predisposes to atrial fibrillation. BioRxiv Prepr Serv Biol. 2023:2023.05.18.541326. doi:10.1101/2023.05.18.541326.
3. 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.
4. Brundel BJJM, Ai X, Hills MT, et al. Atrial fibrillation. Nat Rev Dis Primer. 2022;8(1):21. doi:10.1038/s41572-022-00347-9.
5. 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.
6. Scott L, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol. 2019;287:195-200. doi:10.1016/j.ijcard.2018.10.020.
7. Luan Y, Guo Y, Li S, et al. Interleukin-18 among atrial fibrillation patients in the absence of structural heart disease. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol. 2010;12(12):1713-8. doi:10.1093/europace/euq321.
8. Pappritz K, Lin J, El-Shafeey M, et al. Colchicine prevents disease progression in viral myocarditis via modulating the NLRP3 inflammasome in the cardiosplenic axis. ESC Heart Fail. 2022;9(2):925-41. doi:10.1002/ehf2.13845.
9. Ajoolabady A, Nattel S, Lip GYH, et al. Inflammasome Signaling in Atrial Fibrillation: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022;79(23):2349-66. doi:10.1016/j.jacc.2022.03.379.
10. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019;74(1): 104-32. doi:10.1016/j.jacc.2019.01.011.
11. 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.
12. 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.
13. Cheng X, Zhao H, Wen X, et al. NLRP3-inflammasome inhibition by MCC950 attenuates cardiac and pulmonary artery remodelling in heart failure with preserved ejection fraction. Life Sci. 2023;333:122185. doi:10.1016/j.lfs.2023.122185.
14. Testa M, Yeh M, Lee P, et al. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol. 1996;28(4):964-71. doi:10.1016/s0735-1097(96)00268-9.
15. Wang Y, Li Y, Zhang W, et al. NLRP3 Inflammasome: a Novel Insight into Heart Failure. J Cardiovasc Transl Res. 2023;16(1):166-76. doi:10.1007/s12265-022-10286-1.
16. Buckley LF, Carbone S, Trankle CR, et al. Effect of Interleukin-1 Blockade on Left Ventricular Systolic Performance and Work: A Post Hoc Pooled Analysis of 2 Clinical Trials. J Cardiovasc Pharmacol. 2018;72(1):68-70. doi:10.1097/FJC.0000000000000591.
17. Trankle CR, Canada JM, Cei L, et al. Usefulness of Canakinumab to Improve Exercise Capacity in Patients With Long-Term Systolic Heart Failure and Elevated C-Reactive Protein. Am J Cardiol. 2018;122(8):1366-70. doi:10.1016/j.amjcard.2018.07.002.
18. Everett BM, Cornel JH, Lainscak M, et al. Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. Circulation. 2019;139(10):1289-99. doi:10.1161/CIRCULATIONAHA.118.038010.
19. Wohlford GF, Van Tassell BW, Billingsley HE, et al. Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure. J Cardiovasc Pharmacol. 2020;77(1):49-60. doi:10.1097/FJC.0000000000000931.
20. 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.
21. Ryabov VV, Gombozhapova AE, Samoilova YuO, et al. NLRP3 inflammasome in the pathogenesis of acute myocardial infarction: a cardiologist's view. Russian Journal of Cardiology. 2024;29(4):5649. (In Russ.) Рябов В. В., Гомбожапова А. Э., Самойлова Ю. О. и др. NLRP3 инфламмасома в патогенезе острого инфаркта миокарда: взгляд кардиолога. Российский кардиологический журнал. 2024;29(4):5649. doi:10.15829/1560-4071-2024-5649.
22. Rajamäki K, Mäyränpää MI, Risco A, et al. p38δ MAPK: A Novel Regulator of NLRP3 Inflammasome Activation With Increased Expression in Coronary Atherogenesis. Arterioscler Thromb Vasc Biol. 2016;36(9):1937-46. doi:10.1161/ATVBAHA.115.307312.
23. Nordeng J, Schandiz H, Solheim S, et al. The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI. Mediators Inflamm. 2021;2021:5525917. doi:10.1155/2021/5525917.
24. Zhu J, Wu S, Hu S, et al. NLRP3 inflammasome expression in peripheral blood monocytes of coronary heart disease patients and its modulation by rosuvastatin. Mol Med Rep. 2019;20(2):1826-36. doi:10.3892/mmr.2019.10382.
25. Akosile W, Voisey J, Lawford B, et al. NLRP3 is associated with coronary artery disease in Vietnam veterans. Gene. 2020;725:144163. doi:10.1016/j.gene.2019.144163.
26. Afrasyab A, Qu P, Zhao Y, et al. Correlation of NLRP3 with severity and prognosis of coronary atherosclerosis in acute coronary syndrome patients. Heart Vessels. 2016;31(8): 1218-29. doi:10.1007/s00380-015-0723-8.
27. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383(19):1838-47. doi:10.1056/NEJMoa2021372.
28. Tardif JC, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497-505. doi:10.1056/NEJMoa1912388.
29. Tucker B, Kurup R, Barraclough J, et al. Colchicine as a Novel Therapy for Suppressing Chemokine Production in Patients With an Acute Coronary Syndrome: A Pilot Study. Clin Ther. 2019;41(10):2172-81. doi:10.1016/j.clinthera.2019.07.015.
30. Mewton N, Roubille F, Bresson D, et al. Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction. Circulation. 2021;144(11):859-69. doi:10.1161/CIRCULATIONAHA.121.056177.
31. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-31. doi:10.1056/NEJMoa1707914.
32. Abbate A, Van Tassell BW, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013;111(10):1394-400. doi:10.1016/j.amjcard.2013.01.287.
33. Abbate A, Kontos MC, Grizzard JD, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010;105(10):1371-7.e1. doi:10.1016/j.amjcard.2009.12.059.
34. Mauro AG, Bonaventura A, Vecchié A, et al. The Role of NLRP3 Inflammasome in Pericarditis: Potential for Therapeutic Approaches. JACC Basic Transl Sci. 2021;6(2): 137-50. doi:10.1016/j.jacbts.2020.11.016.
35. Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet Lond Engl. 2014;383(9936):2232-7. doi:10.1016/S0140-6736(13)62709-9.
36. Imazio M, Andreis A, De Ferrari GM, et al. Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study. Eur J Prev Cardiol. 2020;27(9):956-64. doi:10.1177/2047487319879534.
37. Brucato A, Imazio M, Gattorno M, et al. Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016;316(18):1906-12. doi:10.1001/jama.2016.15826.
38. Collini V, Andreis A, De Biasio M, et al. Efficacy of colchicine in addition to anakinra in patients with recurrent pericarditis. Open Heart. 2024;11(1):e002599. doi:10.1136/openhrt-2023-002599.
39. Klein AL, Imazio M, Cremer P, et al. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med. 2021;384(1):31-41. doi:10.1056/NEJMoa2027892.
40. Toldo S, Kannan H, Bussani R, et al. Formation of the inflammasome in acute myocarditis. Int J Cardiol. 2014;171(3):e119-21. doi:10.1016/j.ijcard.2013.12.137.
41. Han RO, Ray PE, Baughman KL, et al. Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction. Biochem Biophys Res Commun. 1991;181(2):520-3. doi:10.1016/0006-291x(91)91219-3.
42. Malandrino D, Bello F, Lopalco G, et al. Effectiveness and safety of IL1 inhibition with anakinra in chronic refractory idiopathic myocarditis. Intern Emerg Med. 2024;19(2):583-8. doi:10.1007/s11739-023-03514-2.
43. Kerneis M, Cohen F, Combes A, et al. Rationale and design of the ARAMIS trial: Anakinra versus placebo, a double blind randomized controlled trial for the treatment of acute myocarditis. Arch Cardiovasc Dis. 2023;116(10):460-6. doi:10.1016/j.acvd.2023.07.004.
44. Van Tassell BW, Trankle CR, Canada JM, et al. IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2018;11(8):e005036. doi:10.1161/CIRCHEARTFAILURE.118.005036.
45. Leung YY, Yao Hui LL, Kraus VB. Colchicine-Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45(3):341-50. doi:10.1016/j.semarthrit.2015.06.013.
46. Deftereos S, Giannopoulos G, Angelidis C, et al. Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study. Circulation. 2015;132(15):1395-403. doi:10.1161/CIRCULATIONAHA.115.017611.
47. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149(1):e1-e156. doi:10.1161/CIR.0000000000001193.
48. Kim SR, Lee SG, Kim SH, et al. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020;11(1):2127. doi:10.1038/s41467-020-15983-6.