Воспалительный ответ при ишемическом-реперфузионном повреждении миокарда и направленная доставка противовоспалительных агентов в зону инфаркта

Данный обзор посвящен механизмам воспаления при ишемическом-реперфузионном повреждении (ИРП) миокарда, охватывающим весь комплекс локальных процессов, включающих в себя распознавание повреждения, инициацию и разрешение воспаления в ткани сердечной мышцы. В ходе обзора современных данных из литературных источников авторами раскрываются функции различных медиаторов воспаления, указываются основные патогенетические молекулярные мишени и их основные сигнальные пути. Ведущая роль в регуляции воспалительного ответа ассоциированных с повреждением аларминов, рецепторов врожденного иммунитета, инфламмасом, ядерных транскрипционных факторов, белков комплемента, провоспалительных цитокинов и хемокинов, адгезионных молекул и матриксных металлопротеиназ, а также клеточных эффекторов воспаления, представленных клетками крови, костного мозга и окружающих тканей, указывает на перспективные направления для поиска механизмов, подавляющих воспаление. Поэтому вторая часть обзора посвящена таргетной доставке противовоспалительных препаратов в зону ИРП миокарда. Здесь рассматриваются два основных способа направленной доставки противовоспалительных активных веществ — пассивный, с помощью наночастиц, проникающих благодаря повышенной проницаемости в зоне ИРП, и активный, при котором наночастицы-носители активного вещества дополнительно модифицированы специфически тропными к ишемизированному миокарду направляющими лигандами.

1. Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6(3):606-19. doi:10.1161/HHF.0b013e318291329a.

2. Shalnova SA, Drapkina OM, Kutsenko VA, et al. Myocardial infarction in the population of some Russian regions and its prognostic value. Russian Journal of Cardiology. 2022;27(6):4952. (In Russ.) Шальнова С. А., Драпкина О. М., Куценко В. А. и др. Инфаркт миокарда в популяции некоторых регионов России и его прогностическое значение. Российский кардиологический журнал. 2022;27(6):4952. doi:10.15829/1560-4071-2022-4952.

3. Shi H, Xia Y, Cheng Y, et al. Global burden of ischaemic heart disease from 2022 to 2050: projections of incidence, prevalence, deaths, and disability-adjusted life years. Eur Heart J Qual Care Clin Outcomes. 2025;11(4):355-66. doi:10.1093/ehjqcco/qcae049.

4. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357(11):1121-35. doi:10.1056/NEJMra071667.

5. Shlyakhto EV, Petrishchev NN, Galagudza MM, et al. Cardioprotection: fundamental and clinical aspects. SPb.: NP-Print, 2013. p. 399. (In Russ.) Шляхто Е. В., Петрищев Н. Н., Галагудза М. М. и др. Кардиопротекция: фундаментальные и клинические аспекты. CПб.: НП-Принт, 2013. с. 399.

6. Saxena A, Russo I, Frangogiannis NG. Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges. Transl Res. 2016;167(1):152-66. doi:10.1016/j.trsl.2015.07.002.

7. Prabhu SD, Frangogiannis NG. The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. Circ Res. 2016;119(1):91-112. doi:10.1161/CIRCRESAHA.116.303577.

8. Vandervelde S, van Amerongen MJ, Tio RA, et al. Increased inflammatory response and neovascularization in reperfused vs. non-reperfused murine myocardial infarction. Cardiovasc Pathol. 2006;15(2):83-90. doi:10.1016/j.carpath.2005.10.006.

9. Matter MA, Paneni F, Libby P, et al. Inflammation in acute myocardial infarction: the good, the bad and the ugly. Eur Heart J. 2024;45(2):89-103. doi:10.1093/eurheartj/ehad486.

10. Ridker PM, MacFadyen JG, Everett BM, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018;391(10118):319-28. doi:10.1016/S0140-6736(17)32814-3.

11. 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.

12. Galagudza M, Korolev D, Postnov V, et al. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles. Int J Nanomedicine. 2012;7:1671-8. doi:10.2147/IJN.S29511.

13. Luo Q, Sun W, Li Z, et al. Biomaterials-mediated targeted therapeutics of myocardial ischemia-reperfusion injury. Biomaterials. 2023;303:122368. doi: 10.1016/j.biomaterials.2023.122368.

14. Hilgendorf I, Frantz S, Frangogiannis NG. Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities. Circ Res. 2024;134(12):1718-51. doi:10.1161/CIRCRESAHA.124.323658.

15. Yoshimura C, Nagasaka A, Kurose H, Nakaya M. Efferocytosis during myocardial infarction. J Biochem. 2020;168(1):1-6. doi:10.1093/jb/mvaa051.

16. Reichardt IM, Robeson KZ, Regnier M, Davis J. Controlling cardiac fibrosis through fibroblast state space modulation. Cell Signal. 2021;79:109888. doi:10.1016/j.cellsig.2020.109888.

17. Ongstad EL, Gourdie RG. Can heart function lost to disease be regenerated by therapeutic targeting of cardiac scar tissue? Semin Cell Dev Biol. 2016;58:41-54. doi:10.1016/j.semcdb.2016.05.020.

18. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-6. doi:10.1126/science.1230719.

19. Shilenko LA, Karpov AA, Veretennikova EI, Galagudza MM. The role of neuro-inflammatory in the pathogenesis of brain edema and hemorrhagic transformation in ischemic stroke: mechanisms and therapeutic target. Translational Medicine. 2023;10(6):566-80. (In Russ.) Шиленко Л. А., Карпов А. А., Веретенникова Е. И., Галагудза М. М. Роль нейровоспаления в патогенезе отека головного мозга и геморрагической трансформации при ишемическом инсульте: механизмы и терапевтические мишени. Трансляционная медицина. 2023;10(6):566-80. doi:10.18705/2311-4495-2023-10-6-566-5.

20. Kiełbowski K, Skórka P, Plewa P, et al. The Role of Alarmins in the Pathogenesis of Atherosclerosis and Myocardial Infarction. Curr Issues Mol Biol. 2024;46(8):8995-9015. doi:10.3390/cimb46080532.

21. Wahid A, Wen J, Yang Q, et al. Serum HMGB1 is a biomarker for acute myocardial infarction with or without heart failure. Clin Transl Sci. 2023;16(11):2299-309. doi:10.1111/cts.13630.

22. Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54(2):91-102. doi:10.1038/s12276-022-00736-w.

23. Raucci A, Di Maggio S, Scavello F, et al. The Janus face of HMGB1 in heart disease: a necessary update. Cell Mol Life Sci. 2019;76(2):211-29. doi:10.1007/s00018-018-2930-9.

24. Nakamura Y, Suzuki S, Shimizu T, et al. High Mobility Group Box 1 Promotes Angiogenesis from Bone Marrow-derived Endothelial Progenitor Cells after Myocardial Infarction. J Atheroscler Thromb. 2015;22(6):570-81. doi:10.5551/jat.27235.

25. Frevert CW, Felgenhauer J, Wygrecka M, et al. Danger-Associated Molecular Patterns Derived From the Extracellular Matrix Provide Temporal Control of Innate Immunity. J Histochem Cytochem. 2018;66(4):213-27. doi:10.1369/0022155417740880.

26. Timmers L, Pasterkamp G, de Hoog VC, et al. The innate immune response in reperfused myocardium. Cardiovasc Res. 2012;94(2):276-83. doi:10.1093/cvr/cvs018.

27. Vogel CW. The Role of Complement in Myocardial Infarction Reperfusion Injury: An Underappreciated Therapeutic Target. Front Cell Dev Biol. 2020;8:606407. doi:10.3389/fcell.2020.606407.

28. van der Pouw Kraan TC, Bernink FJ, Yildirim C, et al. Systemic toll-like receptor and interleukin-18 pathway activation in patients with acute ST elevation myocardial infarction. J Mol Cell Cardiol. 2014;67:94-102. doi:10.1016/j.yjmcc.2013.12.021.

29. Arslan F, Smeets MB, O'Neill LA, et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation. 2010;121(1):80-90. doi:10.1161/CIRCULATIONAHA.109.880187.

30. Ha T, Hu Y, Liu L, et al. TLR2 ligands induce cardioprotection against ischaemia/reperfusion injury through a PI3K/Akt-dependent mechanism. Cardiovasc Res. 2010;87(4):694-703. doi:10.1093/cvr/cvq116.

31. Pradillo JM, Fernández-López D, García-Yébenes I, et al. Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning. J Neurochem. 2009;109(1):287-94. doi:10.1111/j.1471-4159.2009.05972.x.

32. de Kleijn DPV, Chong SY, Wang X, et al. Toll-like receptor 7 deficiency promotes survival and reduces adverse left ventricular remodelling after myocardial infarction. Cardiovasc Res. 2019;115(12):1791-803. doi:10.1093/cvr/cvz057.

33. Frangogiannis NG. The Many Faces of NLRs in Macrophage Biology. JACC Basic Transl Sci. 2023;8(5):497-500. doi:10.1016/j.jacbts.2023.02.004.

34. Que X, Zheng S, Song Q, et al. Fantastic voyage: The journey of NLRP3 inflammasome activation. Genes Dis. 2023;11(2):819-29. doi:10.1016/j.gendis.2023.01.009.

35. Wu JW, Lan Q, Zhang DS, et al. Frontiers and Hotspot Evolution of NLRP3 Inflammasome in Myocardial Infarction Research: A Bibliometric Analysis From 2013 to 2024. Cardiovasc Ther. 2025;2025:5178894. doi:10.1155/cdr/5178894.

36. Chen Y, Bao S, Ding Y, et al. Colchicine inhibits myocardial pyroptosis and reduces myocardial cell injury after myocardial infarction through the ESR1-PI3K-Akt-NF-κB signaling pathway. Int Immunopharmacol. 2025;156:114732. doi:10.1016/j.intimp.2025.114732.

37. Zhang KZ, Shen XY, Wang M, et al. Retinol-Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3. J Am Heart Assoc. 2021;10(22):e022011. doi:10.1161/JAHA.121.022011.

38. Toldo S, Marchetti C, Mauro AG, et al. Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse. Int J Cardiol. 2016;209:215-20. doi:10.1016/j.ijcard.2016.02.043.

39. Louwe MC, Olsen MB, Kaasbøll OJ, et al. Absence of NLRP3 Inflammasome in Hematopoietic Cells Reduces Adverse Remodeling After Experimental Myocardial Infarction. JACC Basic Transl Sci. 2020;5(12):1210-24. doi:10.1016/j.jacbts.2020.09.013.

40. Wang B, Jiang T, Qi Y, et al. AGE-RAGE Axis and Cardiovascular Diseases: Pathophysiologic Mechanisms and Prospects for Clinical Applications. Cardiovasc Drugs Ther. 2024 Nov 5. doi:10.1007/s10557-024-07639-0.

41. Duan T, Du Y, Xing C, et al. Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity. Front Immunol. 2022;13:812774. doi:10.3389/fimmu.2022.812774.

42. Gordon JW, Shaw JA, Kirshenbaum LA. Multiple facets of NF-κB in the heart: to be or not to NF-κB. Circ Res. 2011;108(9):1122-32. doi:10.1161/CIRCRESAHA.110.226928.

43. Zhang XQ, Tang R, Li L, et al. Cardiomyocyte-specific p65 NF-κB deletion protects the injured heart by preservation of calcium handling. Am J Physiol Heart Circ Physiol. 2013;305(7):H1089-97. doi:10.1152/ajpheart.00067.2013.

44. Timmers L, van Keulen JK, Hoefer IE, et al. Targeted deletion of nuclear factor kappaB p50 enhances cardiac remodeling and dysfunction following myocardial infarction. Circ Res. 2009;104(5):699-706. doi:10.1161/CIRCRESAHA.108.189746.

45. Lugrin J, Parapanov R, Milano G, et al. The systemic deletion of interleukin-1α reduces myocardial inflammation and attenuates ventricular remodeling in murine myocardial infarction. Sci Rep. 2023;13(1):4006. doi:10.1038/s41598-023-30662-4.

46. Hilfiker-Kleiner D, Shukla P, Klein G, et al. Continuous glycoprotein-130-mediated signal transducer and activator of transcription-3 activation promotes inflammation, left ventricular rupture, and adverse outcome in subacute myocardial infarction. Circulation. 2010;122(2):145-55. doi: 10.1161/CIRCULATIONAHA.109.933127.

47. Wang J, Seo MJ, Deci MB, et al. Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction. Int J Nanomedicine. 2018;13:6441-51. doi:10.2147/IJN.S178650.

48. Kurrelmeyer KM, Michael LH, Baumgarten G, et al. Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction. Proc Natl Acad Sci U.S.A. 2000;97(10):5456-61. doi:10.1073/pnas.070036297.

49. Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ Res. 2015;116(7):1254-68. doi:10.1161/CIRCRESAHA.116.302317.

50. Azzawi M, Hasleton PS, Kan SW, et al. Distribution of myocardial macrophages in the normal human heart. J Anat. 1997;191(3):417-23. doi:10.1046/j.1469-7580.1997.19130417.x.

51. Epelman S, Lavine KJ, Beaudin AE, et al. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity. 2014;40(1):91-104. doi:10.1016/j.immuni.2013.11.019.

52. Li W, Hsiao HM, Higashikubo R, et al. Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling. JCI Insight. 2016;1(12):e87315. doi:10.1172/jci.insight.87315.

53. Singh M, Saini HK. Resident cardiac mast cells and ischemia-reperfusion injury. J Cardiovasc Pharmacol Ther. 2003;8(2):135-48. doi:10.1177/107424840300800207.

54. Yan X, Anzai A, Katsumata Y, et al. Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J Mol Cell Cardiol. 2013;62:24-35. doi:10.1016/j.yjmcc.2013.04.023.

55. Vafadarnejad E, Rizzo G, Krampert L, et al. Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction. Circ Res. 2020;127(9):e232-49. doi:10.1161/CIRCRESAHA.120.317200.

56. Savchenko AS, Borissoff JI, Martinod K, et al. VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice. Blood. 2014;123(1):141-8. doi:10.1182/blood-2013-07-514992.

57. Horckmans M, Ring L, Duchene J, et al. Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J. 2017;38(3):187-97. doi:10.1093/eurheartj/ehw002.

58. Jung K, Kim P, Leuschner F, et al. Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res. 2013;112(6):891-9. doi:10.1161/CIRCRESAHA.111.300484.

59. Thomas G, Tacke R, Hedrick CC, Hanna RN. Nonclassical patrolling monocyte function in the vasculature. Arterioscler Thromb Vasc Biol. 2015;35(6):1306-16. doi:10.1161/ATVBAHA.114.304650.

60. van Amerongen MJ, Harmsen MC, van Rooijen N, et al. Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am J Pathol. 2007;170(3):818-29. doi:10.2353/ajpath.2007.060547.

61. Kanuri B, Sreejit G, Biswas P, et al. Macrophage heterogeneity in myocardial infarction: Evolution and implications for diverse therapeutic approaches. iScience. 2024;27(7):110274. doi:10.1016/j.isci.2024.110274.

62. Zouggari Y, Ait-Oufella H, Bonnin P, et al. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med. 2013;19(10):1273-80. doi:10.1038/nm.3284.

63. Daseke MJ 2nd, Tenkorang MAA, Chalise U, et al. Cardiac fibroblast activation during myocardial infarction wound healing: Fibroblast polarization after MI. Matrix Biol. 2020;91-92:109-16. doi:10.1016/j.matbio.2020.03.010.

64. Bujak M, Frangogiannis NG. The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res. 2007;74(2):184-95. doi:10.1016/j.cardiores.2006.10.002.

65. Krishnamurthy P, Rajasingh J, Lambers E, et al. IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR. Circ Res. 2009;104(2):e9-18. doi:10.1161/CIRCRESAHA.108.188243.

66. Zhang Q, Wang Y, Zhu J, et al. Specialized pro-resolving lipid mediators: a key player in resolving inflammation in autoimmune diseases. Sci Bull. 2025;70(5):778-94. doi:10.1016/j.scib.2024.07.049.

67. Kain V, Ingle KA, Colas RA, et al. Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. J Mol Cell Cardiol. 2015;84:24-35. doi:10.1016/j.yjmcc.2015.04.003.

68. Kain V, Liu F, Kozlovskaya V, et al. Resolution Agonist 15-epi-Lipoxin A4 Programs Early Activation of Resolving Phase in Post-Myocardial Infarction Healing. Sci Rep. 2017;7(1):9999. doi:10.1038/s41598-017-10441-8.

69. Gushchin IS. Receptors of specialized pro-resolving mediators — a probable target of pharmacological restoration of homeostasis in allergic inflammation. Immunologiya. 2021;42(3):277-92. (In Russ.) Гущин И. С. Рецепторы специализированных проразрешающих медиаторов — вероятная мишень фармакологического восстановления гомеостаза при аллергическом воспалении. Иммунология. 2021;42(3):277-92. doi:10.33029/0206-4952-2021-42-3-277-292.

70. Zhao BH, Ruze A, Zhao L, et al. The role and mechanisms of microvascular damage in the ischemic myocardium. Cell Mol Life Sci. 2023;80(11):341. doi:10.1007/s00018-023-04998-z.

71. Leuschner F, Dutta P, Gorbatov R, et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol. 2011;29(11):1005-10. doi:10.1038/nbt.1989.

72. Nagaoka K, Matoba T, Mao Y, et al. A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model. PLoS One. 2015;10(7):e0132451. doi:10.1371/journal.pone.0132451.

73. Margulis K, Neofytou EA, Beygui RE, Zare RN. Celecoxib Nanoparticles for Therapeutic Angiogenesis. ACS Nano. 2015;9(9):9416-26. doi:10.1021/acsnano.5b04137.

74. Somasuntharam I, Yehl K, Carroll SL, et al. Knockdown of TNF-α by DNAzyme gold nanoparticles as an anti-inflammatory therapy for myocardial infarction. Biomaterials. 2016;83:12-22. doi:10.1016/j.biomaterials.2015.12.022.

75. Cuadrado I, Piedras MJ, Herruzo I, et al. EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction. Theranostics. 2016;6(4):545-57. doi: 10.7150/thno.13352.

76. Nakano Y, Matoba T, Tokutome M, et al. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation. Sci Rep. 2016;6:29601. doi:10.1038/srep29601.

77. Maranhão RC, Guido MC, de Lima AD, et al. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats. Int J Nanomedicine. 2017;12:3767-84. doi:10.2147/IJN.S129324.

78. Fujiwara M, Matoba T, Koga JI, et al. Nanoparticle incorporating Toll-like receptor 4 inhibitor attenuates myocardial ischaemia-reperfusion injury by inhibiting monocyte-mediated inflammation in mice. Cardiovasc Res. 2019;115(7):1244-55. doi:10.1093/cvr/cvz066.

79. Tokutome M, Matoba T, Nakano Y, et al. Peroxisome proliferator-activated receptor-gamma targeting nanomedicine promotes cardiac healing after acute myocardial infarction by skewing monocyte/macrophage polarization in preclinical animal models. Cardiovasc Res. 2019;115(2):419-31. doi: 10.1093/cvr/cvy200.

80. Yajima S, Miyagawa S, Fukushima S, et al. Prostacyclin Analogue-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats. JACC Basic Transl Sci. 2019;4(3):318-31. doi: 10.1016/j.jacbts.2018.12.006.

81. Richart AL, Reddy M, Khalaji M, et al. Apo AI Nanoparticles Delivered Post Myocardial Infarction Moderate Inflammation. Circ Res. 2020;127(11):1422-36. doi:10.1161/CIRCRESAHA.120.316848.

82. Ikeda G, Matoba T, Ishikita A, et al. Nanoparticle-Mediated Simultaneous Targeting of Mitochondrial Injury and Inflammation Attenuates Myocardial Ischemia-Reperfusion Injury. J Am Heart Assoc. 2021;10(12):e019521. doi:10.1161/JAHA.120.019521.

83. Wang L, Peng Y, Song L, et al. Colchicine-Containing Nanoparticles Attenuates Acute Myocardial Infarction Injury by Inhibiting Inflammation. Cardiovasc Drugs Ther. 2022;36(6):1075-89. doi:10.1007/s10557-021-07239-2.

84. Wang T, Wang Y, Zhang Y, et al. Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis. ACS Appl Mater Interfaces. 2024;16(45):61551-64. doi:10.1021/acsami.4c08155.

85. Karpov AA, Ivkin DYu, Dracheva AV, et al. Rat model of post-infarct heart failure by left coronary artery occlusion: technical aspects, functional and morphological assessment. Biomedicine. 2014;3:32-48. (In Russ.) Карпов А. А., Ивкин Д. Ю., Драчева А. В. и др. Моделирование постинфарктной сердечной недостаточности путем окклюзии левой коронарной артерии у крыс: техника и методы морфофункциональной оценки Биомедицина. 2014;3:32-48.

86. Wang J, Seo MJ, Deci MB, et al. Effect of CCR2 inhibitor-loaded lipid micelles on inflammatory cell migration and cardiac function after myocardial infarction. Int J Nanomedicine. 2018;13:6441-51. doi:10.2147/IJN.S178650.

87. Tartuce LP, Pacheco Brandt F, Dos Santos Pedroso G, et al. 2-methoxy-isobutyl-isonitrile-conjugated gold nanoparticles improves redox and inflammatory profile in infarcted rats. Colloids Surf B Biointerfaces. 2020;192:111012. doi:10.1016/j.colsurfb.2020.111012.

88. Wei Y, Zhu M, Li S, et al. Engineered Biomimetic Nanoplatform Protects the Myocardium Against Ischemia/Reperfusion Injury by Inhibiting Pyroptosis. ACS Appl Mater Interfaces. 2021;13(29):33756-66. doi:10.1021/acsami.1c03421.

89. Huang C, Zhou S, Chen C, et al. Biodegradable Redox-Responsive AIEgen-Based-Covalent Organic Framework Nanocarriers for Long-Term Treatment of Myocardial Ischemia/Reperfusion Injury. Small. 2022;18(47):e2205062. doi:10.1002/smll.202205062.

90. Lan M, Hou M, Yan J, et al. Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury. Nano Res. 2022;15(10):9125-34. doi:10.1007/s12274-022-4553-6.

91. Hou M, Wu X, Zhao Z, et al. Endothelial cell-targeting, ROS-ultrasensitive drug/siRNA co-delivery nanocomplexes mitigate early-stage neutrophil recruitment for the anti-inflammatory treatment of myocardial ischemia reperfusion injury. Acta Biomater. 2022;143:344-55. doi:10.1016/j.actbio.2022.02.018.

92. Weng X, Tan H, Huang Z, et al. Targeted delivery and ROS-responsive release of Resolvin D1 by platelet chimeric liposome ameliorates myocardial ischemia-reperfusion injury. J Nanobiotechnology. 2022;20(1):454. doi:10.1186/s12951-022-01652-x.

93. Tan Y, Wang X, Gu Y, et al. Neutrophil and endothelial cell membranes coassembled roflumilast nanoparticles attenuate myocardial ischemia/reperfusion injury. Nanomedicine. 2024;19(9):779-97. doi:10.2217/nnm-2023-0313.