Sepsis-induced myocardial depression (SIMD), a common complication of sepsis, is one of the main causes of death in patients with sepsis. The pathogenesis of SIMD is complicated, and the process of SIMD remains incompletely understood, with no single or definitive mechanism fully elucidated. Notably, pyroptosis, as a pro-inflammatory programmed cell death, is characterized by Gasdermin-mediated formation of pores on the cell membrane, cell swelling, and cell rupture accompanied by the release of large amounts of inflammatory factors and other cellular contents. Mechanistically, pyroptosis is mainly divided into the canonical pathway mediated by caspase-1 and the non-canonical pathway mediated by caspase-4/5/11. Pyroptosis has been confirmed to participate in various inflammation-associated diseases. In recent years, more and more studies have shown that pyroptosis is also involved in the occurrence and development of SIMD. This article reviews the molecular mechanisms of pyroptosis and its research progress in SIMD, aiming to provide novel strategies and targets for the treatment of SIMD.
WEN Ri, ZHANG Tie-Ning, YANG Ni, LIU Chun-Feng.
Recent research on pyroptosis in sepsis-induced myocardial depression[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(7): 774-781 https://doi.org/10.7499/j.issn.1008-8830.2312039
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参考文献
1 Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8): 801-810. PMID: 26903338. PMCID: PMC4968574. DOI: 10.1001/jama.2016.0287. 2 Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study[J]. Lancet, 2020, 395(10219): 200-211. PMID: 31954465. PMCID: PMC6970225. DOI: 10.1016/S0140-6736(19)32989-7. 3 Martin L, Derwall M, Al Zoubi S, et al. The septic heart: current understanding of molecular mechanisms and clinical implications[J]. Chest, 2019, 155(2): 427-437. PMID: 30171861. DOI: 10.1016/j.chest.2018.08.1037. 4 Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases[J]. Nat Rev Cardiol, 2024, 21(4): 219-237. PMID: 37923829. DOI: 10.1038/s41569-023-00946-3. 5 Huston HC, Anderson MJ, Fink SL. Pyroptosis and the cellular consequences of gasdermin pores[J]. Semin Immunol, 2023, 69: 101803. PMID: 37437353. PMCID: PMC10530493. DOI: 10.1016/j.smim.2023.101803. 6 Broz P, Pelegrín P, Shao F. The gasdermins, a protein family executing cell death and inflammation[J]. Nat Rev Immunol, 2020, 20(3): 143-157. PMID: 31690840. DOI: 10.1038/s41577-019-0228-2. 7 Yu P, Zhang X, Liu N, et al. Pyroptosis: mechanisms and diseases[J]. Signal Transduct Target Ther, 2021, 6(1): 128. PMID: 33776057. PMCID: PMC8005494. DOI: 10.1038/s41392-021-00507-5. 8 Zhai Z, Yang F, Xu W, et al. Attenuation of rheumatoid arthritis through the inhibition of tumor necrosis factor-induced caspase 3/gasdermin E-Mediated pyroptosis[J]. Arthritis Rheumatol, 2022, 74(3): 427-440. PMID: 34480835. PMCID: PMC9305212. DOI: 10.1002/art.41963. 9 Zheng Z, Deng W, Bai Y, et al. The lysosomal rag-ragulator complex licenses RIPK1 and caspase-8-mediated pyroptosis by Yersinia[J]. Science, 2021, 372(6549): eabg0269. PMID: 35058659. PMCID: PMC8769499. DOI: 10.1126/science.abg0269. 10 Zhou Z, He H, Wang K, et al. Granzyme a from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells[J]. Science, 2020, 368(6494): eaaz7548. PMID: 32299851. DOI: 10.1126/science.aaz7548. 11 Sollberger G, Choidas A, Burn GL, et al. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps[J]. Sci Immunol, 2018, 3(26): eaar6689. PMID: 30143555. DOI: 10.1126/sciimmunol.aar6689. 12 Wang L, Sharif H, Vora SM, et al. Structures and functions of the inflammasome engine[J]. J Allergy Clin Immunol, 2021, 147(6): 2021-2029. PMID: 34092352. PMCID: PMC8597577. DOI: 10.1016/j.jaci.2021.04.018. 13 Vande Walle L, Lamkanfi M. Drugging the NLRP3 inflammasome: from signalling mechanisms to therapeutic targets[J]. Nat Rev Drug Discov, 2024, 23(1): 43-66. PMID: 38030687. DOI: 10.1038/s41573-023-00822-2. 14 Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. PMID: 31036962. PMCID: PMC7807242. DOI: 10.1038/s41577-019-0165-0. 15 Paik S, Kim JK, Silwal P, et al. An update on the regulatory mechanisms of NLRP3 inflammasome activation[J]. Cell Mol Immunol, 2021, 18(5): 1141-1160. PMID: 33850310. PMCID: PMC8093260. DOI: 10.1038/s41423-021-00670-3. 16 Downs KP, Nguyen H, Dorfleutner A, et al. An overview of the non-canonical inflammasome[J]. Mol Aspects Med, 2020, 76: 100924. PMID: 33187725. PMCID: PMC7808250. DOI: 10.1016/j.mam.2020.100924. 17 Wright SS, Vasudevan SO, Rathinam VA. Mechanisms and consequences of noncanonical inflammasome-mediated pyroptosis[J]. J Mol Biol, 2022, 434(4): 167245. PMID: 34537239. PMCID: PMC8844060. DOI: 10.1016/j.jmb.2021.167245. 18 黄薇. UCP2通过调控NLRP3炎症小体通路改善脓毒症心肌损伤的机制研究[D]. 北京: 北京协和医学院, 2021. 19 Busch K, Kny M, Huang N, et al. Inhibition of the NLRP3/IL-1β axis protects against sepsis-induced cardiomyopathy[J]. J Cachexia Sarcopenia Muscle, 2021, 12(6): 1653-1668. PMID: 34472725. PMCID: PMC8718055. DOI: 10.1002/jcsm.12763. 20 Song C, Zhang Y, Pei Q, et al. HSP70 alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial dysfunction-initiated NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes[J]. Burns Trauma, 2022, 10: tkac043. PMID: 36439706. PMCID: PMC9684341. DOI: 10.1093/burnst/tkac043. 21 Dai S, Ye B, Zhong L, et al. GSDMD mediates LPS-induced septic myocardial dysfunction by regulating ROS-dependent NLRP3 inflammasome activation[J]. Front Cell Dev Biol, 2021, 9: 779432. PMID: 34820388. PMCID: PMC8606561. DOI: 10.3389/fcell.2021.779432. 22 Joshi S, Kundu S, Priya VV, et al. Anti-inflammatory activity of carvacrol protects the heart from lipopolysaccharide-induced cardiac dysfunction by inhibiting pyroptosis via NLRP3/Caspase1/Gasdermin D signaling axis[J]. Life Sci, 2023, 324: 121743. PMID: 37120013. DOI: 10.1016/j.lfs.2023.121743. 23 梁欢. ALDH2通过抑制caspase-11介导的非经典途径细胞焦亡减轻脓毒血症心肌损伤[D]. 蚌埠: 蚌埠医学院, 2022. 24 Gao Y, Shi H, Dong Z, et al. Current knowledge of pyroptosis in heart diseases[J]. J Mol Cell Cardiol, 2022, 171: 81-89. PMID: 35868567. DOI: 10.1016/j.yjmcc.2022.07.005. 25 Zhang W, Xu X, Kao R, et al. Cardiac fibroblasts contribute to myocardial dysfunction in mice with sepsis: the role of NLRP3 inflammasome activation[J]. PLoS One, 2014, 9(9): e107639. PMID: 25216263. PMCID: PMC4162616. DOI: 10.1371/journal.pone.0107639. 26 Rong J, Tao X, Lin Y, et al. Loss of hepatic angiotensinogen attenuates sepsis-induced myocardial dysfunction[J]. Circ Res, 2021, 129(5): 547-564. PMID: 34238019. DOI: 10.1161/CIRCRESAHA.120.318075. 27 Wu D, Shi L, Li P, et al. Intermedin1-53 protects cardiac fibroblasts by inhibiting NLRP3 inflammasome activation during sepsis[J]. Inflammation, 2018, 41(2): 505-514. PMID: 29192367. DOI: 10.1007/s10753-017-0706-2. 28 Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy[J]. Nat Rev Cardiol, 2021, 18(6): 424-434. PMID: 33473203. DOI: 10.1038/s41569-020-00492-2. 29 Wang L, Zhao H, Xu H, et al. Targeting the TXNIP-NLRP3 interaction with PSSM1443 to suppress inflammation in sepsis-induced myocardial dysfunction[J]. J Cell Physiol, 2021, 236(6): 4625-4639. PMID: 33452697. DOI: 10.1002/jcp.30186. 30 Zhao M, Zheng Z, Zhang P, et al. IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis[J]. iScience, 2023, 26(9): 107544. PMID: 37636037. PMCID: PMC10450523. DOI: 10.1016/j.isci.2023.107544. 31 Alarcón MML, Ruocco JF, Ferreira F, et al. Toll-like receptor 4 and NLRP3 caspase 1-interleukin-1β-axis are not involved in colon ascendens stent peritonitis-associated heart disease[J]. Shock, 2018, 50(4): 483-492. PMID: 30216298. DOI: 10.1097/SHK.0000000000001059. 32 Li S, Guo Z, Zhang ZY. Protective effects of NLRP3 inhibitor MCC950 on sepsis-induced myocardial dysfunction[J]. J Biol Regul Homeost Agents, 2021, 35(1): 141-150. PMID: 33550789. DOI: 10.23812/20-662-A. 33 Habimana O, Modupe Salami O, Peng J, et al. Therapeutic implications of targeting pyroptosis in cardiac-related etiology of heart failure[J]. Biochem Pharmacol, 2022, 204: 115235. PMID: 36044938. DOI: 10.1016/j.bcp.2022.115235. 34 O'Riordan CE, Purvis GSD, Collotta D, et al. Bruton's tyrosine kinase inhibition attenuates the cardiac dysfunction caused by cecal ligation and puncture in mice[J]. Front Immunol, 2019, 10: 2129. PMID: 31552054. PMCID: PMC6743418. DOI: 10.3389/fimmu.2019.02129. 35 Su ZD, Wei XB, Fu YB, et al. Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes[J]. Ann Transl Med, 2021, 9(5): 413. PMID: 33842634. PMCID: PMC8033388. DOI: 10.21037/atm-20-8196. 36 Rahim I, Sayed RK, Fernández-Ortiz M, et al. Melatonin alleviates sepsis-induced heart injury through activating the Nrf2 pathway and inhibiting the NLRP3 inflammasome[J]. Naunyn Schmiedebergs Arch Pharmacol, 2021, 394(2): 261-277. PMID: 32936353. DOI: 10.1007/s00210-020-01972-5. 37 Wei S, Xiao Z, Huang J, et al. Disulfiram inhibits oxidative stress and NLRP3 inflammasome activation to prevent LPS-induced cardiac injury[J]. Int Immunopharmacol, 2022, 105: 108545. PMID: 35091339. DOI: 10.1016/j.intimp.2022.108545. 38 Qiu J, Xiao X, Gao X, et al. Ulinastatin protects against sepsis?induced myocardial injury by inhibiting NLRP3 inflammasome activation[J]. Mol Med Rep, 2021, 24(4): 730. PMID: 34414461. PMCID: PMC8404092. DOI: 10.3892/mmr.2021.12369. 39 Li Q, Zhang M, Zhao Y, et al. Irisin protects against LPS-stressed cardiac damage through inhibiting inflammation, apoptosis, and pyroptosis[J]. Shock, 2021, 56(6): 1009-1018. PMID: 34779800. DOI: 10.1097/SHK.0000000000001775. 40 Dai S, Ye B, Chen L, et al. Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation[J]. Phytother Res, 2021, 35(9): 5203-5213. PMID: 34131970. DOI: 10.1002/ptr.7191. 41 Wei A, Liu J, Li D, et al. Syringaresinol attenuates sepsis-induced cardiac dysfunction by inhibiting inflammation and pyroptosis in mice[J]. Eur J Pharmacol, 2021, 913: 174644. PMID: 34801532. DOI: 10.1016/j.ejphar.2021.174644. 42 Zhao H, Lin X, Chen Q, et al. Quercetin inhibits the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve sepsis-induced cardiomyopathy[J]. Toxicol Appl Pharmacol, 2023, 477: 116672. PMID: 37648089. DOI: 10.1016/j.taap.2023.116672. 43 Guo T, Jiang ZB, Tong ZY, et al. Shikonin ameliorates LPS-induced cardiac dysfunction by SIRT1-dependent inhibition of NLRP3 inflammasome[J]. Front Physiol, 2020, 11: 570441. PMID: 33178042. PMCID: PMC7596688. DOI: 10.3389/fphys.2020.570441. 44 Li N, Zhou H, Wu H, et al. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3[J]. Redox Biol, 2019, 24: 101215. PMID: 31121492. PMCID: PMC6529775. DOI: 10.1016/j.redox.2019.101215. 45 Ji T, Liu Q, Yu L, et al. GAS6 attenuates sepsis-induced cardiac dysfunction through NLRP3 inflammasome-dependent mechanism[J]. Free Radic Biol Med, 2024, 210: 195-211. PMID: 37979891. DOI: 10.1016/j.freeradbiomed.2023.11.007. 46 Teng Y, Li N, Wang Y, et al. NRF2 inhibits cardiomyocyte pyroptosis via regulating CTRP1 in sepsis-induced myocardial injury[J]. Shock, 2022, 57(4): 590-599. PMID: 34907120. DOI: 10.1097/SHK.0000000000001901. 47 Feng D, Guo L, Liu J, et al. DDX3X deficiency alleviates LPS-induced H9c2 cardiomyocytes pyroptosis by suppressing activation of NLRP3 inflammasome[J]. Exp Ther Med, 2021, 22(6): 1389. PMID: 34650637. PMCID: PMC8506920. DOI: 10.3892/etm.2021.10825. 48 Wang X, Li XL, Qin LJ. The lncRNA XIST/miR-150-5p/c-Fos axis regulates sepsis-induced myocardial injury via TXNIP-modulated pyroptosis[J]. Lab Invest, 2021, 101(9): 1118-1129. PMID: 34045679. DOI: 10.1038/s41374-021-00607-4. 49 Pan L, Yan B, Zhang J, et al. Mesenchymal stem cells-derived extracellular vesicles-shuttled microRNA-223-3p suppress lipopolysaccharide-induced cardiac inflammation, pyroptosis, and dysfunction[J]. Int Immunopharmacol, 2022, 110: 108910. PMID: 35978499. DOI: 10.1016/j.intimp.2022.108910. 50 Wen R, Zhang TN, Zhang T, et al. A novel long noncoding RNA-lncRNA-AABR07066529.3 alleviates inflammation, apoptosis, and pyroptosis by inhibiting MyD88 in lipopolysaccharide-induced myocardial depression[J]. FASEB J, 2023, 37(8): e23063. PMID: 37401890. DOI: 10.1096/fj.202201680R. 51 Lv W, Liu H, Wang X, et al. Circ_0003907 modulates sepsis-induced myocardial injury via enhancing MYD88/NLRP3/NF-κB axis by sponging miR-944[J]. Shock, 2024, 61(5): 705-711. PMID: 38010112. DOI: 10.1097/SHK.0000000000002271. 52 An L, Yang T, Zhong Y, et al. Molecular pathways in sepsis-induced cardiomyocyte pyroptosis: novel finding on long non-coding RNA ZFAS1/miR-138-5p/SESN2 axis[J]. Immunol Lett, 2021, 238: 47-56. PMID: 34271014. DOI: 10.1016/j.imlet.2021.07.003. 53 Liu JJ, Li Y, Yang MS, et al. SP1-induced ZFAS1 aggravates sepsis-induced cardiac dysfunction via miR-590-3p/NLRP3-mediated autophagy and pyroptosis[J]. Arch Biochem Biophys, 2020, 695: 108611. PMID: 33002446. DOI: 10.1016/j.abb.2020.108611.
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