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REVIEW

Research Progress on the Mechanism of Sepsis Induced Myocardial Injury

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Pages 4275-4290 | Published online: 26 Jul 2022

References

  • Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):775–787. doi:10.1001/jama.2016.0289
  • Shankar-Hari M, Harrison DA, Rubenfeld GD, Rowan K. Epidemiology of sepsis and septic shock in critical care units: comparison between sepsis-2 and sepsis-3 populations using a national critical care database. Br J Anaesth. 2017;119(4):626–636.
  • Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311(13):1308–1316.
  • Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319(1):62–75.
  • Fleischmann-Struzek C, Mellhammar L, Rose N, et al. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1552–1562.
  • Fleischmann C, Scherag A, Adhikari NK, et al. Assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. Am J Respir Crit Care Med. 2016;193(3):259–272.
  • Lin GL, McGinley JP, Drysdale SB, Pollard AJ. Epidemiology and immune pathogenesis of viral sepsis. Front Immunol. 2018;9:2147.
  • Fleischmann C, Reichert F. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child. 2021;106(8):745–752.
  • 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. Lancet. 2020;395(10219):200–211.
  • Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018;392(10141):75–87. doi:10.1016/S0140-6736(18)30696-2
  • Gauer R, Forbes D, Boyer N. Sepsis: diagnosis and management. Am Fam Physician. 2020;101(7):409–418.
  • Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013;50(1):23–36. doi:10.3109/10408363.2013.764490
  • Merx MW, Weber C. Sepsis and the heart. Circulation. 2007;116(7):793–802. doi:10.1161/CIRCULATIONAHA.106.678359
  • Genga KR, Russell JA. Update of sepsis in the intensive care unit. J Innate Immun. 2017;9(5):441–455. doi:10.1159/000477419
  • Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi:10.1001/jama.2016.0287
  • Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;18(6):424–434.
  • Lv X, Wang H. Pathophysiology of sepsis-induced myocardial dysfunction. Mil Med Res. 2016;3:30.
  • Li F, Lang F, Zhang H, Xu L, Wang Y, Hao E. Role of TFEB mediated autophagy, oxidative stress, inflammation, and cell death in endotoxin induced myocardial toxicity of young and aged mice. Oxid Med Cell Longev. 2016;2016:5380319.
  • Yang F, Zhao LN, Sun Y, Chen Z. Levosimendan as a new force in the treatment of sepsis-induced cardiomyopathy: mechanism and clinical application. J Int Med Res. 2019;47(5):1817–1828.
  • Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 2006;6(11):813–822.
  • Mahidhara R, Billiar TR. Apoptosis in sepsis. Crit Care Med. 2000;28(4 Suppl):N105–113.
  • Fernandes CJ Jr, Akamine N, Knobel E. Myocardial depression in sepsis. Shock. 2008;30(Suppl 1):14–17.
  • Yang D, Jiang Y, Qian H, Liu X, Mi L. Silencing Cardiac Troponin I-interacting kinase reduces lipopolysaccharide-induced sepsis-induced myocardial dysfunction in rat by regulating apoptosis-related proteins. Biomed Res Int. 2021;2021:5520051.
  • Wang L, Wang Z, Liu X, et al. Effects of extracellular histones on left ventricular diastolic function and potential mechanisms in mice with sepsis. Am J Transl Res. 2022;14(1):150–165.
  • Favory R, Neviere R. Significance and interpretation of elevated troponin in septic patients. Crit Care. 2006;10(4):224.
  • Meng F, Lai H, Luo Z, et al. Effect of xuefu zhuyu decoction pretreatment on myocardium in sepsis rats. Evid-Based Compl Alt Med. 2018;2018:2939307.
  • Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495–516.
  • Li Y, Sun G, Wang L. MiR-21 participates in LPS-induced myocardial injury by targeting Bcl-2 and CDK6. Inflamm res. 2022;71(2):205–214.
  • Yang Z, Liu Y, Deng W, et al. Hesperetin attenuates mitochondria-dependent apoptosis in lipopolysaccharide-induced H9C2 cardiomyocytes. Mol Med Rep. 2014;9(5):1941–1946.
  • Xu P, Zhang WQ, Xie J, Wen YS, Zhang GX, Lu SQ. Shenfu injection prevents sepsis-induced myocardial injury by inhibiting mitochondrial apoptosis. J Ethnopharmacol. 2020;261:113068.
  • Luo S, Huang X, Liu S, Zhang L, Cai X, Chen B. Long non-coding RNA small nucleolar RNA host gene 1 alleviates sepsis-associated myocardial injury by modulating the miR-181a-5p/XIAP axis in vitro. Ann Clin Lab Sci. 2021;51(2):231–240.
  • Reed JC. Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med. 2001;7(7):314–319.
  • Xie WJ, Hou G, Wang L, Wang SS, Xiong XX. Astaxanthin suppresses lipopolysaccharide‑induced myocardial injury by regulating MAPK and PI3K/AKT/mTOR/GSK3β signaling. Mol Med Rep. 2020;22(4):3338–3346.
  • Zhang T, Yin YC, Ji X, et al. AT1R knockdown confers cardioprotection against sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway in rats. J Cell Biochem. 2020;121(1):25–42.
  • Xin Y, Tang L, Chen J, Chen D, Wen W, Han F. Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1. Int J Mol Med. 2021;47(3):45.
  • Martin EL, Ranieri VM. Phosphorylation mechanisms in intensive care medicine. Intensive Care Med. 2011;37(1):7–18.
  • Zhang M, Wang X, Bai B, Zhang R, Li Y, Wang Y. Oxymatrine protects against sepsis-induced myocardial injury via inhibition of the TNF-α/p38-MAPK/caspase-3 signaling pathway. Mol Med Rep. 2016;14(1):551–559.
  • Meng X, Harken AH. The interaction between Hsp70 and TNF-alpha expression: a novel mechanism for protection of the myocardium against post-injury depression. Shock. 2002;17(5):345–353.
  • Shang X, Lin K, Yu R, et al. Resveratrol protects the myocardium in sepsis by activating the phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian target of rapamycin (mTOR) pathway and inhibiting the nuclear factor-κB (NF-κB) signaling pathway. Med Sci Monitor. 2019;25:9290–9298.
  • Ge C, Liu J, Dong S. miRNA-214 protects sepsis-induced myocardial injury. Shock. 2018;50(1):112–118.
  • Liu J, Li J, Tian P, et al. H2S attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism. Exp Ther Med. 2019;17(5):4064–4072.
  • An R, Zhao L, Xi C, et al. Melatonin attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism. Basic Res Cardiol. 2016;111(1):8.
  • Fu C, Xu Q, Tang S, et al. The mobilization of splenic reservoir myeloid-derived suppressor cells in sepsis-induced myocardial injury. Am J Transl Res. 2020;12(11):7114–7126.
  • Li Y, Zhang L, Zhang P, Hao Z. Dehydrocorydaline protects against sepsis-induced myocardial injury through modulating the TRAF6/NF-κB pathway. Front Pharmacol. 2021;12:709604.
  • Zhang Y, Xu X, Ceylan-Isik AF, et al. Ablation of Akt2 protects against lipopolysaccharide-induced cardiac dysfunction: role of Akt ubiquitination E3 ligase TRAF6. J Mol Cell Cardiol. 2014;74:76–87.
  • Zheng Z, Ma H, Zhang X, et al. Enhanced glycolytic metabolism contributes to cardiac dysfunction in polymicrobial sepsis. J Infect Dis. 2017;215(9):1396–1406.
  • Wang SM, Liu GQ, Xian HB, Si JL, Qi SX, Yu YP. LncRNA NEAT1 alleviates sepsis-induced myocardial injury by regulating the TLR2/NF-κB signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23(11):4898–4907.
  • Ouyang H, Tan Y, Li Q, et al. MicroRNA-208-5p regulates myocardial injury of sepsis mice via targeting SOCS2-mediated NF-κB/HIF-1α pathway. Int Immunopharmacol. 2020;81:106204.
  • An R, Feng J, Xi C, Xu J, Sun L. miR-146a attenuates sepsis-induced myocardial dysfunction by suppressing IRAK1 and TRAF6 via targeting ErbB4 expression. Oxid Med Cell Longev. 2018;2018:7163057.
  • Xing C, Xu L, Yao Y. Beneficial role of oleuropein in sepsis-induced myocardial injury. Possible involvement of GSK-3beta/NF-kB pathway. Acta cirurgica brasileira. 2021;36(1):e360107.
  • Li X, Cheng Q, Li J, He Y, Tian P, Xu C. Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats. Exp Ther Med. 2017;14(3):2153–2161.
  • Wang X, Zingarelli B, O’Connor M, et al. Overexpression of Hsp20 prevents endotoxin-induced myocardial dysfunction and apoptosis via inhibition of NF-kappaB activation. J Mol Cell Cardiol. 2009;47(3):382–390.
  • Chen DD, Wang HW, Cai XJ. Transcription factor Sp1 ameliorates sepsis-induced myocardial injury via ZFAS1/Notch signaling in H9C2 cells. Cytokine. 2021;140:155426.
  • Li N, Zhou H, Wu H, et al. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol. 2019;24:101215.
  • Zhang WX, He BM, Wu Y, Qiao JF, Peng ZY. Melatonin protects against sepsis-induced cardiac dysfunction by regulating apoptosis and autophagy via activation of SIRT1 in mice. Life Sci. 2019;217:8–15.
  • Han D, Li X, Li S, et al. Reduced silent information regulator 1 signaling exacerbates sepsis-induced myocardial injury and mitigates the protective effect of a liver X receptor agonist. Free Radic Biol Med. 2017;113:291–303.
  • Chen DD, Wang HW, Cai XJ. Long non-coding RNA ZFAS1 alleviates sepsis-induced myocardial injury via target miR-34b-5p/SIRT1. Innate Immun. 2021;27(5):377–387.
  • Zhu Y, Sun A, Meng T, Li H. Protective role of long noncoding RNA CRNDE in myocardial tissues from injury caused by sepsis through the microRNA-29a/SIRT1 axis. Life Sci. 2020;255:117849.
  • Ni SY, Xu WT, Liao GY, Wang YL, Li J. LncRNA HOTAIR promotes LPS-induced inflammation and apoptosis of cardiomyocytes via Lin28-Mediated PDCD4 stability. Inflammation. 2021;44(4):1452–1463.
  • Zhai Y, Ding N. MicroRNA-194 participates in endotoxemia induced myocardial injury via promoting apoptosis. Eur Rev Med Pharmacol Sci. 2018;22(7):2077–2083.
  • Wang J, Xin S, Yang R, Jiang J, Qiao Y. Knockdown of lncRNA LUCAT1 attenuates sepsis‑induced myocardial cell injury by sponging miR-642a. Mamm Genome. 2021;32(6):457–465.
  • Yang YP, Zhao JQ, Gao HB, et al. Tannic acid alleviates lipopolysaccharide‑induced H9C2 cell apoptosis by suppressing reactive oxygen species‑mediated endoplasmic reticulum stress. Mol Med Rep. 2021;24(1):e34.
  • Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104–107.
  • Kakihana Y, Ito T, Nakahara M, Yamaguchi K, Yasuda T. Sepsis-induced myocardial dysfunction: pathophysiology and management. J Intensive Care. 2016;4:22.
  • Takasu O, Gaut JP, Watanabe E, et al. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med. 2013;187(5):509–517.
  • Unuma K, Aki T, Funakoshi T, Yoshida K, Uemura K. Cobalt protoporphyrin accelerates TFEB activation and lysosome reformation during LPS-induced septic insults in the rat heart. PLoS One. 2013;8(2):e56526.
  • Larche J, Lancel S, Hassoun SM, et al. Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality. J Am Coll Cardiol. 2006;48(2):377–385.
  • Ni R, Zheng D, Wang Q, et al. Deletion of capn4 protects the heart against endotoxemic injury by preventing ATP synthase disruption and inhibiting mitochondrial superoxide generation. Circ Heart Fail. 2015;8(5):988–996.
  • Zhou Q, Xie M, Zhu J, et al. PINK1 contained in huMSC-derived exosomes prevents cardiomyocyte mitochondrial calcium overload in sepsis via recovery of mitochondrial Ca(2+) efflux. Stem Cell Res Ther. 2021;12(1):269.
  • Liu Z, Pan H, Zhang Y, et al. Ginsenoside-Rg1 attenuates sepsis-induced cardiac dysfunction by modulating mitochondrial damage via the P2X7 receptor-mediated Akt/GSK-3β signaling pathway. J Biochem Mol Toxicol. 2022;36(1):e22885.
  • Hu Y, Yan JB, Zheng MZ, et al. Mitochondrial aldehyde dehydrogenase activity protects against lipopolysaccharide‑induced cardiac dysfunction in rats. Mol Med Rep. 2015;11(2):1509–1515.
  • Zuo T, Tang Q, Zhang X, Shang F. MicroRNA-410-3p binds to TLR2 and alleviates myocardial mitochondrial dysfunction and chemokine production in LPS-Induced sepsis. Mol Ther Nucleic Acids. 2020;22:273–284.
  • Shang X, Li J, Yu R, et al. Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin signaling pathway. J Mol Histol. 2019;50(2):91–103.
  • Fang X, Wang J. [Role of mitochondrial dysfunction in the pathogenesis of septic cardiomyopathy]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018;30(2):189–192. Chinese.
  • De Kock I, Van Daele C, Poelaert J. Sepsis and septic shock: pathophysiological and cardiovascular background as basis for therapy. Acta Clin Belg. 2010;65(5):323–329.
  • Liang D, Huang A, Jin Y, et al. Protective effects of exogenous NaHS against sepsis-induced myocardial mitochondrial injury by enhancing the PGC-1α/NRF2 pathway and mitochondrial biosynthesis in mice. Am J Transl Res. 2018;10(5):1422–1430.
  • Wang Y, Jasper H, Toan S, Muid D, Chang X, Zhou H. Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury. Redox Biol. 2021;45:102049.
  • Piquereau J, Godin R, Deschenes S, et al. Protective role of PARK2/Parkin in sepsis-induced cardiac contractile and mitochondrial dysfunction. Autophagy. 2013;9(11):1837–1851.
  • Li J, Shi W, Zhang J, Ren L. To explore the protective mechanism of PTEN-Induced Kinase 1 (PINK1)/Parkin mitophagy-mediated extract of Periplaneta americana on lipopolysaccharide-induced cardiomyocyte injury. Med Sci Monitor. 2019;25:1383–1391.
  • Shi J, Chen Y, Zhi H, An H, Hu Z. Levosimendan protects from sepsis-inducing cardiac dysfunction by suppressing inflammation, oxidative stress and regulating cardiac mitophagy via the PINK-1-Parkin pathway in mice. Ann Transl Med. 2022;10(4):212.
  • Zhang E, Zhao X, Zhang L, et al. Minocycline promotes cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy to prevent sepsis-induced cardiac dysfunction by Akt/mTOR signaling. Apoptosis. 2019;24(3–4):369–381.
  • Mao JY, Su LX, Li DK, Zhang HM, Wang XT, Liu DW. The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism. Ann Transl Med. 2021;9(3):259.
  • Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res. 2017;120(11):1812–1824.
  • Zhao P, Kuai J, Gao J, Sun L, Wang Y, Yao L. Delta opioid receptor agonist attenuates lipopolysaccharide-induced myocardial injury by regulating autophagy. Biochem Biophys Res Commun. 2017;492(1):140–146.
  • Jia J, Gong X, Zhao Y, et al. Autophagy enhancing contributes to the organ protective effect of alpha-lipoic acid in septic rats. Front Immunol. 2019;10:1491.
  • Luo Y, Fan C, Yang M, et al. CD74 knockout protects against LPS-induced myocardial contractile dysfunction through AMPK-Skp2-SUV39H1-mediated demethylation of BCLB. Br J Pharmacol. 2020;177(8):1881–1897.
  • Turdi S, Han X, Huff AF, et al. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy. Free Radic Biol Med. 2012;53(6):1327–1338.
  • Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases. EMBO J. 2021;40(19):e108863.
  • Mizushima N, Levine B. Autophagy in human diseases. N Engl J Med. 2020;383(16):1564–1576.
  • Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368(7):651–662.
  • Yuan MJ, Wang T. The new mechanism of Ghrelin/GHSR-1a on autophagy regulation. Peptides. 2020;126:170264.
  • Yu T, Liu D, Gao M, et al. Dexmedetomidine prevents septic myocardial dysfunction in rats via activation of α7nAChR and PI3K/Akt- mediated autophagy. Biomed Pharmacother. 2019;120:109231.
  • Qiao Y, Wang L, Hu T, Yin D, He H, He M. Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy augmentation. Front Pharmacol. 2021;12:659015.
  • Jiao Y, Li W, Wang W, et al. Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock. Crit Care. 2020;24(1):380.
  • Kaplan MJ, Radic M. Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol. 2012;189(6):2689–2695.
  • Chen P, An Q, Huang Y, Zhang M, Mao S. Prevention of endotoxin-induced cardiomyopathy using sodium tanshinone IIA sulfonate: involvement of augmented autophagy and NLRP3 inflammasome suppression. Eur J Pharmacol. 2021;909:174438.
  • Wu B, Song H, Fan M, et al. Luteolin attenuates sepsis‑induced myocardial injury by enhancing autophagy in mice. Int J Mol Med. 2020;45(5):1477–1487.
  • Di S, Wang Z, Hu W, et al. The protective effects of melatonin against LPS-induced septic myocardial injury: a potential role of AMPK-mediated autophagy. Front Endocrinol (Lausanne). 2020;11:162.
  • Loffler AS, Alers S, Dieterle AM, et al. Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy. 2011;7(7):696–706.
  • Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132–141. doi:10.1038/ncb2152
  • Ren J, Xu X, Wang Q, Ren SY, Dong M, Zhang Y. Permissive role of AMPK and autophagy in adiponectin deficiency-accentuated myocardial injury and inflammation in endotoxemia. J Mol Cell Cardiol. 2016;93:18–31. doi:10.1016/j.yjmcc.2016.02.002
  • Tang R, Jia L, Li Y, Zheng J, Qi P. Narciclasine attenuates sepsis-induced myocardial injury by modulating autophagy. Aging. 2021;13(11):15151–15163. doi:10.18632/aging.203078
  • Tasselli L, Zheng W, Chua KF. SIRT6: novel mechanisms and links to aging and disease. Trends Endocrinol Metab. 2017;28(3):168–185. doi:10.1016/j.tem.2016.10.002
  • Yuan X, Chen G, Guo D, Xu L, Gu Y. Polydatin alleviates septic myocardial injury by promoting SIRT6-Mediated autophagy. Inflammation. 2020;43(3):785–795. doi:10.1007/s10753-019-01153-4
  • Cain BS, Meldrum DR, Dinarello CA, et al. Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function. Crit Care Med. 1999;27(7):1309–1318. doi:10.1097/00003246-199907000-00018
  • Wang M, Markel TA, Meldrum DR. Interleukin 18 in the heart. Shock. 2008;30(1):3–10. doi:10.1097/SHK.0b013e318160f215
  • Chen X, Peng Y, Ge S, Li Y. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis. Burns Trauma. 2013;1(3):109–121. doi:10.4103/2321-3868.123072
  • Zhou Q, Pan X, Wang L, Wang X, Xiong D. The protective role of neuregulin-1: a potential therapy for sepsis-induced cardiomyopathy. Eur J Pharmacol. 2016;788:234–240. doi:10.1016/j.ejphar.2016.06.042
  • Okuhara Y, Yokoe S, Iwasaku T, et al. Interleukin-18 gene deletion protects against sepsis-induced cardiac dysfunction by inhibiting PP2A activity. Int J Cardiol. 2017;243:396–403. doi:10.1016/j.ijcard.2017.04.082
  • Zhao P, Wang Y, Zeng S, Lu J, Jiang TM, Li YM. Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice. Immunopharmacol Immunotoxicol. 2015;37(5):428–433. doi:10.3109/08923973.2015.1080266
  • Yang C, Xia W, Liu X, Lin J, Wu A. Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction. Int J Mol Med. 2019;44(2):417–426. doi:10.3892/ijmm.2019.4232
  • Dai S, Ye B, Zhong L, et al. GSDMD mediates LPS-Induced septic myocardial dysfunction by regulating ROS-dependent NLRP3 inflammasome activation. Front Cell Develop Biol. 2021;9:779432. doi:10.3389/fcell.2021.779432
  • Yang L, Zhang H, Chen P. Sulfur dioxide attenuates sepsis-induced cardiac dysfunction via inhibition of NLRP3 inflammasome activation in rats. Nitric Oxide. 2018;81:11–20. doi:10.1016/j.niox.2018.09.005
  • Guo T, Jiang ZB, Tong ZY, Zhou Y, Chai XP, Xiao XZ. Shikonin ameliorates LPS-Induced cardiac dysfunction by SIRT1-dependent inhibition of NLRP3 inflammasome. Front Physiol. 2020;11:570441. doi:10.3389/fphys.2020.570441
  • Wei S, Xiao Z, Huang J, Peng Z, Zhang B, Li W. Disulfiram inhibits oxidative stress and NLRP3 inflammasome activation to prevent LPS-induced cardiac injury. Int Immunopharmacol. 2022;105:108545. doi:10.1016/j.intimp.2022.108545
  • Wu M, Huang Z, Huang W, et al. microRNA-124-3p attenuates myocardial injury in sepsis via modulating SP1/HDAC4/HIF-1α axis. Cell Death Discov. 2022;8(1):40. doi:10.1016/j.phrs.2021.105781
  • Xie S, Qi X, Wu Q, et al. Inhibition of 5-lipoxygenase is associated with downregulation of the leukotriene B4 receptor 1/ Interleukin-12p35 pathway and ameliorates sepsis-induced myocardial injury. Free Radic Biol Med. 2021;166:348–357. doi:10.1016/j.freeradbiomed.2021.02.034
  • Zhang M, Wang X, Wang X, et al. Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signaling in rat septic shock. Mol Med Rep. 2013;7(4):1293–1299. doi:10.3892/mmr.2013.1315
  • He H, Chang X, Gao J, Zhu L, Miao M, Yan T. Salidroside mitigates sepsis-induced myocarditis in rats by regulating IGF-1/PI3K/Akt/GSK-3β signaling. Inflammation. 2015;38(6):2178–2184. doi:10.1007/s10753-015-0200-7
  • Niu J, Azfer A, Kolattukudy PE. Protection against lipopolysaccharide-induced myocardial dysfunction in mice by cardiac-specific expression of soluble Fas. J Mol Cell Cardiol. 2008;44(1):160–169. doi:10.1016/j.yjmcc.2007.09.016
  • Ning L, Rong J, Zhang Z, Xu Y. Therapeutic approaches targeting renin-angiotensin system in sepsis and its complications. Pharmacol Res. 2021;167:105409. doi:10.1016/j.phrs.2020.105409
  • Chen S, Fan B. Myricetin protects cardiomyocytes from LPS-induced injury. Herz. 2018;43(3):265–274. doi:10.1007/s00059-017-4556-3
  • Coldewey SM, Rogazzo M, Collino M, Patel NS, Thiemermann C. Inhibition of IκB kinase reduces the multiple organ dysfunction caused by sepsis in the mouse. Dis Model Mech. 2013;6(4):1031–1042.
  • Chen H, Liu Q, Liu X, Jin J. Berberine attenuates septic cardiomyopathy by inhibiting TLR4/NF-κB signalling in rats. Pharm Biol. 2021;59(1):121–128. doi:10.1080/13880209.2021.1877736
  • Xu X, Rui S, Chen C, et al. Protective effects of astragalus polysaccharide nanoparticles on septic cardiac dysfunction through inhibition of TLR4/NF-κB signaling pathway. Int J Biol Macromol. 2020;153:977–985. doi:10.1016/j.ijbiomac.2019.10.227
  • Zhang Y, Zhang J, Xu K, et al. Helium protects against lipopolysaccharide-induced cardiac dysfunction in mice via suppressing toll-like receptor 4-nuclear factor κB-tumor necrosis factor-Alpha/ Interleukin-18 signaling. Chin J Physiol. 2020;63(6):276–285. doi:10.4103/CJP.CJP_66_20
  • Xie J, Zhang L, Fan X, Dong X, Zhang Z, Fan W. MicroRNA-146a improves sepsis-induced cardiomyopathy by regulating the TLR-4/NF-κB signaling pathway. Exp Ther Med. 2019;18(1):779–785. doi:10.3892/etm.2019.7657
  • Chang C, Hu L, Sun S, et al. Regulatory role of the TLR4/JNK signaling pathway in sepsis‑induced myocardial dysfunction. Mol Med Rep. 2021;23(5). doi:10.3892/mmr.2021.11973
  • Shyni GL, Renjitha J, Somappa S, Raghu,KG. Zerumin A attenuates the inflammatory responses in LPS-stimulated H9c2 cardiomyoblasts. J Biochem Mol Toxicol. 2021;35(6):1–11. doi:10.1002/jbt.22777
  • Zhang J, Wang M, Ye J, et al. The anti-inflammatory mediator resolvin E1 protects mice against lipopolysaccharide-induced heart injury. Front Pharmacol. 2020;11:203. doi:10.3389/fphar.2020.00203
  • Meldrum DR. Tumor necrosis factor in the heart. Am J Physiol. 1998;274(3):R577–595. doi:10.1152/ajpregu.1998.274.3.R577
  • Cao C, Zhang Y, Chai Y, et al. Attenuation of sepsis-induced cardiomyopathy by regulation of MicroRNA-23b is mediated through targeting of MyD88-Mediated NF-κB activation. Inflammation. 2019;42(3):973–986. doi:10.1007/s10753-019-00958-7
  • Song YX, Ou YM, Zhou JY. Gracillin inhibits apoptosis and inflammation induced by lipopolysaccharide (LPS) to alleviate cardiac injury in mice via improving miR-29a. Biochem Biophys Res Commun. 2020;523(3):580–587. doi:10.1016/j.bbrc.2019.11.129
  • Shi XJ, Jin Y, Xu WM, Shen Q, Li J, Chen K. MicroRNA-23a reduces lipopolysaccharide-induced cellular apoptosis and inflammatory cytokine production through Rho-associated kinase 1/sirtuin-1/nuclear factor-kappa B crosstalk. Chin Med J. 2021;134(7):829–839. doi:10.1097/CM9.0000000000001369
  • Wang Z, Bu L, Yang P, Feng S, Xu F. Alleviation of sepsis‑induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of p‑S6K and activation of the p‑AMPK pathway. Mol Med Rep. 2019;20(3):2511–2518. doi:10.3892/mmr.2019.10520
  • Zhang J, Liu Y, Liu L. Hyperoside prevents sepsis-associated cardiac dysfunction through regulating cardiomyocyte viability and inflammation via inhibiting miR-21. Biomed Pharmacother. 2021;138:111524. doi:10.1016/j.biopha.2021.111524
  • Pei X, Wu Y, Yu H, et al. Protective role of lncRNA TTN-AS1 in sepsis-induced myocardial injury via miR-29a/E2F2 axis. Cardiovasc Drugs Ther. 2021;36:399–412. doi:10.1007/s10557-021-07244-5
  • Luo YY, Yang ZQ, Lin XF, et al. Knockdown of lncRNA PVT1 attenuated macrophage M1 polarization and relieved sepsis induced myocardial injury via miR-29a/HMGB1 axis. Cytokine. 2021;143:155509. doi:10.1016/j.cyto.2021.155509
  • Dai Q, Hong Y, Li J. PVT1 knockdown inhibited the biological behavior of LPS-induced cardiac fibroblasts by regulating miR-24. Genes Genomics. 2021;43(9):1003–1009. doi:10.1007/s13258-021-01104-0
  • Feng F, Qi Y, Dong C, Yang C. PVT1 regulates inflammation and cardiac function via the MAPK/NF-κB pathway in a sepsis model. Exp Ther Med. 2018;16(6):4471–4478. doi:10.3892/etm.2018.6814
  • Liu Y, Liu L, Zhang J. Protective role of matrine in sepsis-associated cardiac dysfunction through regulating the lncRNA PTENP1/miR-106b-5p axis. Biomed Pharmacother. 2021;134:111112. doi:10.1016/j.biopha.2020.111112
  • Fang Y, Hu J, Wang Z, et al. LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis. Biomed Pharmacother. 2018;105:1183–1191. doi:10.1016/j.biopha.2018.06.007
  • Ling L, Zhi L, Wang H, Deng Y, Gu C. MicroRNA-181b inhibits inflammatory response and reduces myocardial injury in sepsis by downregulating HMGB1. Inflammation. 2021;44(4):1263–1273. doi:10.1007/s10753-020-01411-w
  • Wu P, Kong L, Li J. MicroRNA-494-3p protects rat cardiomyocytes against septic shock via PTEN. Exp Ther Med. 2019;17(3):1706–1716. doi:10.3892/etm.2018.7116
  • Yao Y, Xu K, Sun Y, et al. MiR-215-5p inhibits the inflammation injury in septic H9c2 by regulating ILF3 and LRRFIP1. Int Immunopharmacol. 2020;78:106000. doi:10.1016/j.intimp.2019.106000
  • Pei Y, Xie S, Li J, Jia B. Bone marrow-mesenchymal stem cell-derived exosomal microRNA-141 targets PTEN and activates β-catenin to alleviate myocardial injury in septic mice. Immunopharmacol Immunotoxicol. 2021;43(5):584–593. doi:10.1080/08923973.2021.1955920
  • Capcha JMC, Rodrigues CE, Moreira RS, et al. Wharton’s jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation. Am J Physiol Regul Integr Comp Physiol. 2020;318(1):R135–R147. doi:10.1152/ajpregu.00098.2018
  • Wang X, Gu H, Qin D, et al. Exosomal miR-223 contributes to mesenchymal stem cell-elicited cardioprotection in polymicrobial sepsis. Sci Rep. 2015;5:13721. doi:10.1038/srep13721
  • Mantzarlis K, Tsolaki V, Zakynthinos E. Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies. Oxid Med Cell Longev. 2017;2017:5985209. doi:10.1155/2017/5985209
  • Neri M, Riezzo I, Pomara C, Schiavone S, Turillazzi E. Oxidative-nitrosative stress and myocardial dysfunctions in sepsis: evidence from the literature and postmortem observations. Mediators Inflamm. 2016;2016:3423450. doi:10.1155/2016/3423450
  • Galley HF. Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth. 2011;107(1):57–64. doi:10.1093/bja/aer093
  • Lowes DA, Thottakam BM, Webster NR, Murphy MP, Galley HF. The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis. Free Radic Biol Med. 2008;45(11):1559–1565. doi:10.1016/j.freeradbiomed.2008.09.003
  • Xianchu L, Lan PZ, Qiufang L, et al. Naringin protects against lipopolysaccharide-induced cardiac injury in mice. Environ Toxicol Pharmacol. 2016;48:1–6. doi:10.1016/j.etap.2016.09.005
  • Wang F, Jin Z, Shen K, et al. Butyrate pretreatment attenuates heart depression in a mice model of endotoxin-induced sepsis via anti-inflammation and anti-oxidation. Am J Emerg Med. 2017;35(3):402–409. doi:10.1016/j.ajem.2016.11.022
  • Zhang J, Yang Z, Liang Z, et al. Anti-Interleukin-16 neutralizing antibody treatment alleviates sepsis-induced cardiac injury and dysfunction via the nuclear factor Erythroid-2 related factor 2 pathway in mice. Oxid Med Cell Longev. 2021;2021:6616422. doi:10.1155/2021/6616422
  • Li D, Wang M, Ye J, et al. Maresin 1 alleviates the inflammatory response, reduces oxidative stress and protects against cardiac injury in LPS-induced mice. Life Sci. 2021;277:119467. doi:10.1016/j.lfs.2021.119467
  • Hao E, Lang F, Chen Y, et al. Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor. PLoS One. 2013;8(7):e69452. doi:10.1371/journal.pone.0069452
  • Lei S, Zhang Y, Su W, Zhou L, Xu J, Xia ZY. Remifentanil attenuates lipopolysaccharide-induced oxidative injury by downregulating PKCβ2 activation and inhibiting autophagy in H9C2 cardiomyocytes. Life Sci. 2018;213:109–115.
  • Li F, Lang F, Zhang H, et al. Apigenin alleviates endotoxin-induced myocardial toxicity by modulating inflammation, oxidative stress, and autophagy. Oxid Med Cell Longev. 2017;2017:2302896.
  • Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 2021;6(1):128.
  • Zhaolin Z, Guohua L, Shiyuan W, Zuo W. Role of pyroptosis in cardiovascular disease. Cell Prolif. 2019;52(2):e12563.
  • Gao YL, Zhai JH, Chai YF. Recent advances in the molecular mechanisms underlying pyroptosis in sepsis. Mediators Inflamm. 2018;2018:5823823.
  • Wei A, Liu J, Li D, et al. Syringaresinol attenuates sepsis-induced cardiac dysfunction by inhibiting inflammation and pyroptosis in mice. Eur J Pharmacol. 2021;913:174644.
  • Vande Walle L, Lamkanfi M. Pyroptosis. Current Biol. 2016;26(13):R568–R572.
  • Wang Q, Wu J, Zeng Y, et al. Pyroptosis: a pro-inflammatory type of cell death in cardiovascular disease. Clin Chim Acta. 2020;510:62–72.
  • Li Q, Zhang M, Zhao Y, Dong M. Irisin protects against LPS-Stressed cardiac damage through inhibiting inflammation, apoptosis, and pyroptosis. Shock. 2021;56(6):1009–1018.
  • Dai S, Ye B, Chen L, Hong G, Zhao G, Lu Z. Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation. Phytother Res. 2021;35(9):5203–5213.
  • Teng Y, Li N, Wang Y, et al. NRF2 inhibits cardiomyocyte pyroptosis via regulating CTRP1 in sepsis-induced myocardial injury. Shock. 2022;57(4):590–599.
  • Wang X, Li XL, Qin LJ. The lncRNA XIST/miR-150-5p/c-Fos axis regulates sepsis-induced myocardial injury via TXNIP-modulated pyroptosis. Lab Invest. 2021;101(9):1118–1129.
  • An L, Yang T, Zhong Y, Yin Y, Li W, Gao H. Molecular pathways in sepsis-induced cardiomyocyte pyroptosis: novel finding on long non-coding RNA ZFAS1/miR-138-5p/SESN2 axis. Immunol Lett. 2021;238:47–56.
  • Tu GW, Ma JF, Li JK, et al. Exosome-derived from sepsis patients’ blood promoted pyroptosis of cardiomyocytes by regulating miR-885-5p/HMBOX1. Front Cardiovasc med. 2022;9:774193.
  • Marino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 2014;15(2):81–94.
  • Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741–752.
  • Xie Q, Liu Y, Li X. The interaction mechanism between autophagy and apoptosis in colon cancer. Transl Oncol. 2020;13(12):100871.
  • Ding Y, Wang L, Zhao Q, Wu Z, Kong L. MicroRNA‑93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF‑κB signaling pathway. Int J Mol Med. 2019;43(2):779–790.
  • Dannappel M, Vlantis K, Kumari S, et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014;513(7516):90–94.
  • Deretic V. Autophagy in inflammation, infection, and immunometabolism. Immunity. 2021;54(3):437–453.
  • Wang X, Guo Z, Ding Z, Mehta JL. Inflammation, autophagy, and apoptosis after myocardial infarction. J Am Heart Assoc. 2018;7(9):43.
  • Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidative stress and inflammation: what polyphenols can do for us? Oxid Med Cell Longev. 2016;2016:7432797.
  • Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol. 2015;71:40–56.
  • Sul OJ, Ra SW. Quercetin prevents LPS-induced oxidative stress and inflammation by modulating NOX2/ROS/NF-kB in lung epithelial cells. Molecules. 2021;26(22):43.
  • Wiegman CH, Michaeloudes C, Haji G, et al. Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2015;136(3):769–780.
  • Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109.
  • Kesavardhana S, Malireddi RKS, Kanneganti TD. Caspases in cell death, inflammation, and pyroptosis. Annu Rev Immunol. 2020;38:567–595.