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2000
Volume 23, Issue 4
  • ISSN: 1570-1611
  • E-ISSN: 1875-6212

Abstract

Neutrophil elastase (NE), a major protease in neutrophils, is important in promoting inflammation and multiple pathological processes. While NE is released abundantly in ischemia-reperfusion (I/R) injury, the intricate relationship between NE and I/R injury remains unclear. We examine several aspects of how NE is involved in I/R injury. We also discuss the possibility of NE inhibitors used for abbreviating various types of I/R injury, such as myocardial infarction, based on preclinical research and clinical trials. Furthermore, we highlight the key question, the balance of NE and NE inhibitors, and propose new research directions. This review is useful for understanding the intrinsic interplay between NE and I/R injury-related diseases and expects to facilitate the development of effective NE inhibitors applied for I/R injury.

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2025-10-07

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References

  1. PhamC.T.N. Neutrophil serine proteases: Specific regulators of inflammation.Nat. Rev. Immunol.20066754155010.1038/nri1841 16799473
     [Google Scholar]
  2. AhYoung AP, Lin SJ, Gerhardy S, van Lookeren Campagne M, Kirchhofer D. An ancient mechanism of arginine-specific substrate cleavage: What’s ‘up’ with NSP4?Biochimie2019166192610.1016/j.biochi.2019.03.020
     [Google Scholar]
  3. HeinzA. Elastases and elastokines: Elastin degradation and its significance in health and disease.Crit. Rev. Biochem. Mol. Biol.202055325227310.1080/10409238.2020.1768208 32530323
     [Google Scholar]
  4. PolverinoE. Rosales-MayorE. DaleG.E. DembowskyK. TorresA. The role of neutrophil elastase inhibitors in lung diseases.Chest2017152224926210.1016/j.chest.2017.03.056 28442313
     [Google Scholar]
  5. ZhangF. LiY. WuJ. The role of extracellular traps in ischemia reperfusion injury.Front. Immunol.202213102238010.3389/fimmu.2022.1022380 36211432
     [Google Scholar]
  6. VoisinM.B. LeoniG. WoodfinA. Neutrophil elastase plays a non‐redundant role in remodeling the venular basement membrane and neutrophil diapedesis post-ischemia/reperfusion injury.J. Pathol.201924818810210.1002/path.5234 30632166
     [Google Scholar]
  7. ZhaoY. ZhangX. ChenX. WeiY. Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review).Int. J. Mol. Med.20214921510.3892/ijmm.2021.5070 34878154
     [Google Scholar]
  8. EltzschigH.K. EckleT. Ischemia and reperfusion—from mechanism to translation.Nat. Med.201117111391140110.1038/nm.2507 22064429
     [Google Scholar]
  9. ZhangM. LiuQ. MengH. Ischemia-reperfusion injury: Molecular mechanisms and therapeutic targets.Signal Transduct. Target. Ther.2024911210.1038/s41392‑023‑01688‑x 38185705
     [Google Scholar]
  10. SaithongS. SaisornW. DangC.P. VisitchanakunP. ChiewchengcholD. LeelahavanichkulA. <b><i>Candida</i></b> Administration worsens neutrophil extracellular traps in renal ischemia reperfusion injury mice: An impact of gut fungi on acute kidney injury.J. Innate Immun.202214550251710.1159/000521633 35093955
     [Google Scholar]
  11. KiwitA. LuY. LenzM. The dual role of Neutrophil Extracellular Traps (NETs) in sepsis and ischemia-reperfusion injury: Comparative analysis across murine models.Int. J. Mol. Sci.2024257378710.3390/ijms25073787 38612596
     [Google Scholar]
  12. ShepherdH.M. GauthierJ.M. TeradaY. Updated views on neutrophil responses in Ischemia–reperfusion injury.Transplantation2022106122314232410.1097/TP.0000000000004221 35749228
     [Google Scholar]
  13. HeubergerD.M. SchuepbachR.A. Protease-activated receptors (PARs): Mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thromb. J.2019171410.1186/s12959‑019‑0194‑8 30976204
     [Google Scholar]
  14. VidhyaR. AnuradhaC.V. Anti-inflammatory effects of troxerutin are mediated through elastase inhibition.Immunopharmacol. Immunotoxicol.202042542343510.1080/08923973.2020.1806870 32762381
     [Google Scholar]
  15. AlamS.R. NewbyD.E. HenriksenP.A. Role of the endogenous elastase inhibitor, elafin, in cardiovascular injury.Biochem. Pharmacol.201283669570410.1016/j.bcp.2011.11.003 22100985
     [Google Scholar]
  16. SchauerC. JankoC. MunozL.E. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines.Nat. Med.201420551151710.1038/nm.3547 24784231
     [Google Scholar]
  17. OkadaY. NakanishiI. Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G.FEBS Lett.1989249235335610.1016/0014‑5793(89)80657‑X 2544455
     [Google Scholar]
  18. OltmannsU. SukkarM.B. XieS. JohnM. ChungK.F. Induction of human airway smooth muscle apoptosis by neutrophils and neutrophil elastase.Am. J. Respir. Cell Mol. Biol.200532433434110.1165/rcmb.2004‑0321OC 15653931
     [Google Scholar]
  19. ChandlerS. CossinsJ. LuryJ. WellsG. Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein.Biochem. Biophys. Res. Commun.1996228242142910.1006/bbrc.1996.1677 8920930
     [Google Scholar]
  20. DinkelK. DhabharF.S. SapolskyR.M. Neurotoxic effects of polymorphonuclear granulocytes on hippocampal primary cultures.Proc. Natl. Acad. Sci. USA2004101133133610.1073/pnas.0303510101 14684829
     [Google Scholar]
  21. MaslovL.N. PopovS.V. MukhomedzyanovA.V. Reperfusion cardiac injury: Receptors and the signaling mechanisms.Curr. Cardiol. Rev.20221856379 35422224
     [Google Scholar]
  22. ZhangK. KaufmanR.J. From endoplasmic-reticulum stress to the inflammatory response.Nature2008454720345546210.1038/nature07203 18650916
     [Google Scholar]
  23. UlrichM. WorlitzschD. ViglioS. Alveolar inflammation in cystic fibrosis.J. Cyst. Fibros.20109321722710.1016/j.jcf.2010.03.001 20347403
     [Google Scholar]
  24. SköldC.M. LiuX. UminoT. Human neutrophil elastase augments fibroblast-mediated contraction of released collagen gels.Am. J. Respir. Crit. Care Med.199915941138114610.1164/ajrccm.159.4.9805033 10194158
     [Google Scholar]
  25. ZhuY.K. LiuX. WangH. Interactions between monocytes and smooth-muscle cells can lead to extracellular matrix degradation.J. Allergy Clin. Immunol.2001108698999610.1067/mai.2001.120193 11742278
     [Google Scholar]
  26. DolleryC.M. OwenC.A. SukhovaG.K. KrettekA. ShapiroS.D. LibbyP. Neutrophil elastase in human atherosclerotic plaques: Production by macrophages.Circulation2003107222829283610.1161/01.CIR.0000072792.65250.4A 12771009
     [Google Scholar]
  27. YangM. ChenQ. MeiL. Neutrophil elastase promotes neointimal hyperplasia by targeting toll‐like receptor 4 (TLR4)–NF‐κB signalling.Br. J. Pharmacol.2021178204048406810.1111/bph.15583 34076894
     [Google Scholar]
  28. IzawaY. HawkinsB. del ZoppoG. Hemostasis and alterations of the central nervous system.Semin. Thromb. Hemost.201339885687510.1055/s‑0033‑1357490 24166247
     [Google Scholar]
  29. VoisinM.B. PröbstlD. NoursharghS. Venular basement membranes ubiquitously express matrix protein low-expression regions: Characterization in multiple tissues and remodeling during inflammation.Am. J. Pathol.2010176148249510.2353/ajpath.2010.090510 20008148
     [Google Scholar]
  30. WeiX. ZouS. XieZ. EDIL3 deficiency ameliorates adverse cardiac remodelling by neutrophil extracellular traps (NET)-mediated macrophage polarization.Cardiovasc. Res.202211892179219510.1093/cvr/cvab269 34375400
     [Google Scholar]
  31. EngelmannB. MassbergS. Thrombosis as an intravascular effector of innate immunity.Nat. Rev. Immunol.2013131344510.1038/nri3345 23222502
     [Google Scholar]
  32. CollingM.E. TourdotB.E. KanthiY. Inflammation, infection and venous thromboembolism.Circ. Res.2021128122017203610.1161/CIRCRESAHA.121.318225 34110909
     [Google Scholar]
  33. MaoJ.Y. ZhangJ.H. ChengW. ChenJ.W. CuiN. Effects of neutrophil extracellular traps in patients with septic coagulopathy and their interaction with autophagy.Front. Immunol.20211275704110.3389/fimmu.2021.757041 34707618
     [Google Scholar]
  34. MikesB. SinkovitsG. FarkasP. Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura.Thromb. Res.2014133461662110.1016/j.thromres.2014.01.034 24548690
     [Google Scholar]
  35. GisteråA. HanssonG.K. The immunology of atherosclerosis.Nat. Rev. Nephrol.201713636838010.1038/nrneph.2017.51 28392564
     [Google Scholar]
  36. MartinodK. WagnerD.D. Thrombosis: Tangled up in NETs.Blood2014123182768277610.1182/blood‑2013‑10‑463646 24366358
     [Google Scholar]
  37. MaulerM. HerrN. SchoenichenC. Platelet serotonin aggravates myocardial ischemia/reperfusion injury via neutrophil degranulation.Circulation2019139791893110.1161/CIRCULATIONAHA.118.033942 30586717
     [Google Scholar]
  38. TangM. ZhaoX.G. GuY.J. ChenC.Z. An in vitro model for studying neutrophil activation during cardiopulmonary bypass by using a polymerase chain reaction thermocycler.Altern. Lab. Anim.201038321321910.1177/026119291003800307 20602537
     [Google Scholar]
  39. HiguchiD.A. WunT.C. LikertK.M. BrozeG.J.J.Jr The effect of leukocyte elastase on tissue factor pathway inhibitor.Blood19927971712171910.1182/blood.V79.7.1712.1712 1558967
     [Google Scholar]
  40. MassbergS. GrahlL. von BruehlM.L. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.Nat. Med.201016888789610.1038/nm.2184 20676107
     [Google Scholar]
  41. HelmsJ. Clere-JehlR. BianchiniE. Thrombomodulin favors leukocyte microvesicle fibrinolytic activity, reduces NETosis and prevents septic shock-induced coagulopathy in rats.Ann. Intensive Care20177111810.1186/s13613‑017‑0340‑z 29222696
     [Google Scholar]
  42. AdamsS.A. KellyS.L. KirschR.E. RobsonS.C. ShephardE.G. Role of neutrophil membrane proteases in fibrin degradation.Blood Coagul. Fibrinolysis19956869370210.1097/00001721‑199512000‑00001 8825218
     [Google Scholar]
  43. RábaiG. SzilágyiN. SótonyiP. Contribution of neutrophil elastase to the lysis of obliterative thrombi in the context of their platelet and fibrin content.Thromb. Res.20101262e94e10110.1016/j.thromres.2010.05.007 20627279
     [Google Scholar]
  44. HayakawaM. SawamuraA. GandoS. Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase.Surgery2011149222123010.1016/j.surg.2010.06.010 20655560
     [Google Scholar]
  45. WeberC. NoelsH. Atherosclerosis: Current pathogenesis and therapeutic options.Nat. Med.201117111410142210.1038/nm.2538 22064431
     [Google Scholar]
  46. WarnatschA. IoannouM. WangQ. PapayannopoulosV. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis.Science2015349624531632010.1126/science.aaa8064 26185250
     [Google Scholar]
  47. BecariC. DurandM.T. GuimaraesA.O. Elastase-2, a tissue alternative pathway for angiotensin II generation, plays a role in circulatory sympathovagal balance in mice.Front. Physiol.2017817010.3389/fphys.2017.00170 28386233
     [Google Scholar]
  48. GandoS. NanzakiS. MorimotoY. KobayashiS. KemmotsuO. Out-of-hospital cardiac arrest increases soluble vascular endothelial adhesion molecules and neutrophil elastase associated with endothelial injury.Intensive Care Med.2000261384410.1007/s001340050009 10663278
     [Google Scholar]
  49. ZipperleJ. ZieglerB. SchöchlH. Conventional and pro-inflammatory pathways of fibrinolytic activation in non-traumatic hyperfibrinolysis.J. Clin. Med.20221124730510.3390/jcm11247305 36555922
     [Google Scholar]
  50. LiP. LiangS. WangL. GuanX. WangJ. GongP. Predictive value of neutrophil extracellular traps components for 28-day all-cause mortality in patients with cardiac arrest: A pilot observational study.Shock202360566467010.1097/SHK.0000000000002225 37695643
     [Google Scholar]
  51. ChenF. WangD. JiangY. MaH. LiX. WangH. Dexmedetomidine postconditioning alleviates spinal cord ischemia-reperfusion injury in rats via inhibiting neutrophil infiltration, microglia activation, reactive gliosis and CXCL13/CXCR5 axis activation.Int. J. Neurosci.2023133111210.1080/00207454.2021.1881089 33499703
     [Google Scholar]
  52. MuroharaT. GuoJ.P. LeferA.M. Cardioprotection by a novel recombinant serine protease inhibitor in myocardial ischemia and reperfusion injury.J. Pharmacol. Exp. Ther.1995274312461253 7562495
     [Google Scholar]
  53. AuneS.E. YehS.T. KuppusamyP. KuppusamyM.L. KhanM. AngelosM.G. Sivelestat attenuates myocardial reperfusion injury during brief low flow postischemic infusion.Oxid. Med. Cell. Longev.201320131910.1155/2013/279847 23766850
     [Google Scholar]
  54. GengH. ZhangH. ChengL. DongS. Sivelestat ameliorates sepsis-induced myocardial dysfunction by activating the PI3K/AKT/mTOR signaling pathway.Int. Immunopharmacol.202412811146610.1016/j.intimp.2023.111466
     [Google Scholar]
  55. ToldoS. MauroA.G. MarchettiC. Recombinant human Alpha-1 Antitrypsin-Fc fusion protein reduces mouse myocardial inflammatory injury after Ischemia–reperfusion independent of elastase inhibition.J. Cardiovasc. Pharmacol.2016681273210.1097/FJC.0000000000000383 26945157
     [Google Scholar]
  56. HayakawaM. SawamuraA. YanagidaY. Insufficient production of urinary trypsin inhibitor for neutrophil elastase release after cardiac arrest.Shock200829554955210.1097/SHK.0b013e31815cfcd6 17998887
     [Google Scholar]
  57. DingQ. LoganathanS. ZhouP. Alpha-1-antitrypsin protects vascular grafts of brain-dead rats against ischemia/reperfusion injury.J. Surg. Res.202328395396410.1016/j.jss.2022.11.047 36915024
     [Google Scholar]
  58. LiuB. KorkmazB. KraftP. Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats.J. Transl. Med.202321179910.1186/s12967‑023‑04659‑6 37946197
     [Google Scholar]
  59. GrauA.J. SeitzR. ImmelA. Steichen-WiehnC. HackeW. Increased levels of leukocyte elastase in ischemic stroke and in subjects with vascular risk-factors.Cerebrovasc. Dis.199551505410.1159/000107819
     [Google Scholar]
  60. IwatsukiK. KumuraE. YoshimineT. YamamotoK. SatoM. HayakawaT. Increase in jugular levels of polymorphonuclear neutrophil elastase in patients with acute cerebral infarction.Neurol. Res.199820539740210.1080/01616412.1998.11740537 9664584
     [Google Scholar]
  61. DangQ.B. LapergueB. Tran-DinhA. High-density lipoproteins limit neutrophil-induced damage to the blood-brain barrier in vitro.J. Cereb. Blood Flow Metab.201333457558210.1038/jcbfm.2012.206 23299241
     [Google Scholar]
  62. CarboneF. VuilleumierN. BertolottoM. Treatment with recombinant tissue plasminogen activator (r-TPA) induces neutrophil degranulation in vitro via defined pathways.Vascul. Pharmacol.201564162710.1016/j.vph.2014.11.007 25530154
     [Google Scholar]
  63. StoweA.M. Adair-KirkT.L. GonzalesE.R. Neutrophil elastase and neurovascular injury following focal stroke and reperfusion.Neurobiol. Dis.2009351829010.1016/j.nbd.2009.04.006 19393318
     [Google Scholar]
  64. HorinokitaI. HayashiH. YoshizawaR. Possible involvement of progranulin in the protective effect of elastase inhibitor on cerebral ischemic injuries of neuronal and glial cells.Mol. Cell. Neurosci.202111310362510.1016/j.mcn.2021.103625 33933589
     [Google Scholar]
  65. HorinokitaI. HayashiH. OtekiR. Involvement of progranulin and granulin expression in inflammatory responses after cerebral ischemia.Int. J. Mol. Sci.20192020521010.3390/ijms20205210 31640144
     [Google Scholar]
  66. MatayoshiH. HirataT. YamashitaS. Neutrophil elastase inhibitor attenuates hippocampal neuronal damage after transient forebrain ischemia in rats.Brain Res.200912599810610.1016/j.brainres.2008.12.070 19168036
     [Google Scholar]
  67. IkegameY. YamashitaK. HayashiS. YoshimuraS. NakashimaS. IwamaT. Neutrophil elastase inhibitor prevents ischemic brain damage via reduction of vasogenic edema.Hypertens. Res.201033770370710.1038/hr.2010.58 20485441
     [Google Scholar]
  68. WaisbergM. Molina-CruzA. MizuriniD.M. Plasmodium falciparum infection induces expression of a mosquito salivary protein (Agaphelin) that targets neutrophil function and inhibits thrombosis without impairing hemostasis.PLoS Pathog.2014109e100433810.1371/journal.ppat.1004338 25211214
     [Google Scholar]
  69. LeinweberJ. MizuriniD.M. FrancischettiI.M.B. Elastase inhibitor agaphelin protects from acute ischemic stroke in mice by reducing thrombosis, blood–brain barrier damage, and inflammation.Brain Behav. Immun.20219328829810.1016/j.bbi.2020.12.027 33401017
     [Google Scholar]
  70. RostN.S. MeschiaJ.F. GottesmanR. Cognitive impairment and dementia after stroke: Design and rationale for the discovery study.Stroke2021528e499e51610.1161/STROKEAHA.120.031611 34039035
     [Google Scholar]
  71. García-CulebrasA. CuarteroM.I. Peña-MartínezC. Myeloid cells in vascular dementia and Alzheimer’s disease: Possible therapeutic targets?Br. J. Pharmacol.2024181677779810.1111/bph.16159 37282844
     [Google Scholar]
  72. Ramos-CejudoJ. JohnsonA.D. BeiserA. The meutrophil to lymphocyte ratio is associated with the risk of subsequent dementia in the framingham heart study.Front. Aging Neurosci.20211377398410.3389/fnagi.2021.773984 34916927
     [Google Scholar]
  73. GiannelliR. CanaleP. Del CarratoreR. Ultrastructural and molecular investigation on peripheral leukocytes in Alzheimer’s disease patients.Int. J. Mol. Sci.2023249790910.3390/ijms24097909 37175616
     [Google Scholar]
  74. ChoK.S. LeeE.J. KimJ.N. Proteinase 3 induces neuronal cell death through microglial activation.Neurochem. Res.201540112242225110.1007/s11064‑015‑1714‑y 26349766
     [Google Scholar]
  75. ScarffK.L. UngK.S. NandurkarH. CrackP.J. BirdC.H. BirdP.I. Targeted disruption of SPI3/Serpinb6 does not result in developmental or growth defects, leukocyte dysfunction, or susceptibility to stroke.Mol. Cell. Biol.20042494075408210.1128/MCB.24.9.4075‑4082.2004 15082799
     [Google Scholar]
  76. LiF. ZhangY. LiR. Neuronal Serpina3n is an endogenous protector against blood brain barrier damage following cerebral ischemic stroke.J. Cereb. Blood Flow Metab.202343224125710.1177/0271678X221113897 36457151
     [Google Scholar]
  77. PrakashR. MishraR.K. AhmadA. KhanM.A. KhanR. RazaS.S. Sivelestat-loaded nanostructured lipid carriers modulate oxidative and inflammatory stress in human dental pulp and mesenchymal stem cells subjected to oxygen-glucose deprivation.Mater. Sci. Eng. C202112011170010.1016/j.msec.2020.111700 33545859
     [Google Scholar]
  78. AikawaN. IshizakaA. HirasawaH. Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study.Pulm. Pharmacol. Ther.201124554955410.1016/j.pupt.2011.03.001 21540122
     [Google Scholar]
  79. GotoT. IshizakaA. KobayashiF. Importance of tumor necrosis factor-α cleavage process in post-transplantation lung injury in rats.Am. J. Respir. Crit. Care Med.2004170111239124610.1164/rccm.200402‑146OC 15333331
     [Google Scholar]
  80. RehmS.R.T. SmirnovaN.F. MorroneC. Premedication with a cathepsin C inhibitor alleviates early primary graft dysfunction in mouse recipients after lung transplantation.Sci. Rep.201991992510.1038/s41598‑019‑46206‑8 31289357
     [Google Scholar]
  81. MoriH. NagahiroI. OsaragiT. Addition of a neutrophil elastase inhibitor to the organ flushing solution decreases lung reperfusion injury in rat lung transplantation.Eur. J. Cardiothorac. Surg.200732579179510.1016/j.ejcts.2007.07.017 17888675
     [Google Scholar]
  82. IskenderI. SakamotoJ. NakajimaD. Human α1-antitrypsin improves early post-transplant lung function: Pre-clinical studies in a pig lung transplant model.J. Heart Lung Transplant.201635791392110.1016/j.healun.2016.03.006 27095003
     [Google Scholar]
  83. GötzfriedJ. SmirnovaN.F. MorroneC. Preservation with α1-antitrypsin improves primary graft function of murine lung transplants.J. Heart Lung Transplant.20183781021102810.1016/j.healun.2018.03.015 29776812
     [Google Scholar]
  84. JanciauskieneS. WelteT. Well-known and less well-known functions of Alpha-1 antitrypsin. Its role in chronic obstructive pulmonary disease and other disease developments.Ann. Am. Thorac. Soc.201613Suppl. 4S280S28810.1513/AnnalsATS.201507‑468KV 27564662
     [Google Scholar]
  85. YılmazA.H. DoganU. ÖzgülH. Effect of ischemia-reperfusion injury on elafin levels in rat liver.Ulus. Travma Acil Cerrahi Derg.2024302808910.14744/tjtes.2024.32728 38305656
     [Google Scholar]
  86. YamazakiS. TakayamaT. MoriguchiM. Neutrophil elastase inhibitor following liver resection: A matched cohort study.Hepat. Mon.20151511e3123510.5812/hepatmon.31235 26834789
     [Google Scholar]
  87. KawaiM. HaradaN. TakeyamaH. OkajimaK. Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats.Transl. Res.2010155629430410.1016/j.trsl.2010.02.003 20478544
     [Google Scholar]
  88. ChenH.M. ChenJ.C. ShyrM.H. Neutrophil elastase inhibitor (ONO-5046) attenuates reperfusion-induced hepatic microcirculatory derangement, energy depletion and lipid peroxidation in rats.Shock199912646246710.1097/00024382‑199912000‑00008 10588515
     [Google Scholar]
  89. UchidaY. FreitasM.C.S. ZhaoD. BusuttilR.W. Kupiec-WeglinskiJ.W. The inhibition of neutrophil elastase ameliorates mouse liver damage due to ischemia and reperfusion.Liver Transpl.200915893994710.1002/lt.21770 19642132
     [Google Scholar]
  90. HuY. ZhanF. WangY. The Ninj1/Dusp1 axis contributes to liver ischemia reperfusion injury by regulating macrophage activation and neutrophil infiltration.Cell. Mol. Gastroenterol. Hepatol.20231551071108410.1016/j.jcmgh.2023.01.008 36731792
     [Google Scholar]
  91. IshiharaK. YamaguchiY. UchinoS. ICAM-1 signal transduction in cells stimulated with neutrophil elastase.Dig. Dis. Sci.200651112102211210.1007/s10620‑006‑9178‑1 17024574
     [Google Scholar]
  92. SparkenbaughE.M. GaneyP.E. RothR.A. Hypoxia sensitization of hepatocytes to neutrophil elastase-mediated cell death depends on MAPKs and HIF-1α.Am. J. Physiol. Gastrointest. Liver Physiol.20123027G748G75710.1152/ajpgi.00409.2011 22223132
     [Google Scholar]
  93. YamaguchiY. AkizukiE. IchiguchiO. Neutrophil elastase inhibitor reduces neutrophil chemoattractant production after ischemia-reperfusion in rat liver.Gastroenterology1997112255156010.1053/gast.1997.v112.pm9024309 9024309
     [Google Scholar]
  94. DoiK. HoriuchiT. UchinamiM. Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.Eur. J. Surg.2002168850751010.1080/110241502321116541 12549694
     [Google Scholar]
  95. TsujiiS. OkabayashiT. ShigaM. The effect of the neutrophil elastase inhibitor sivelestat on early injury after liver resection.World J. Surg.20123651122112710.1007/s00268‑012‑1501‑8 22366983
     [Google Scholar]
  96. LinasS.L. WhittenburgD. ParsonsP.E. RepineJ.E. Mild renal ischemia activates primed neutrophils to cause acute renal failure.Kidney Int.199242361061610.1038/ki.1992.325 1405339
     [Google Scholar]
  97. Zynek-LitwinM. KuzniarJ. MarchewkaZ. Plasma and urine leukocyte elastase- 1protease inhibitor complex as a marker of early and long-term kidney graft function.Nephrol. Dial. Transplant.20102572346235110.1093/ndt/gfq041 20164046
     [Google Scholar]
  98. TunónH. BohlinL. Anti-inflammatory studies on Menyanthes trifoliata related to the effect shown against renal failure in rats.Phytomedicine19952210311210.1016/S0944‑7113(11)80054‑1 23196151
     [Google Scholar]
  99. MatsuyamaM. HayamaT. FunaoK. The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury.Mol. Med. Rep.20081448949210.3892/mmr.1.4.489 21479437
     [Google Scholar]
  100. SaisornW. SaithongS. PhuengmaungP. Acute kidney injury induced lupus exacerbation through the enhanced neutrophil extracellular traps (and Apoptosis) in Fcgr2b deficient lupus mice with renal ischemia reperfusion injury.Front. Immunol.20211266916210.3389/fimmu.2021.669162 34248948
     [Google Scholar]
  101. WangC.L. WangY. JiangQ.L. DNase I and sivelestat ameliorate experimental hindlimb ischemia-reperfusion injury by eliminating neutrophil extracellular traps.J. Inflamm. Res.20231670772110.2147/JIR.S396049 36852300
     [Google Scholar]
  102. CuongN.T. AbeC. BinhN.H. HaraA. MoritaH. OguraS. Sivelestat improves outcome of crush injury by inhibiting high-mobility group box 1 in rats.Shock2013391899510.1097/SHK.0b013e31827a2412 23247125
     [Google Scholar]
  103. SuzukiT. SakuraiM. SuzukiH. KawamuraT. Endoplasmic reticulum stress is involved in the protective effect of sivelestat sodium hydrate (ONO-5046) in spinal cord ischemia-reperfusion injury.J. Nippon Med. Sch.2023901505710.1272/jnms.JNMS.2023_90‑109 36908128
     [Google Scholar]
  104. WelbournC.R.B. GoldmanG. PatersonI.S. ValeriC.R. SheproD. HechtmanH.B. Neutrophil elastase and oxygen radicals: Synergism in lung injury after hindlimb ischemia.Am. J. Physiol.19912606 Pt 2H1852H1856 2058722
     [Google Scholar]
  105. ForbesT.L. HarrisK.A. JamiesonW.G. DeRoseG. CarsonM. PotterR.F. Leukocyte activity and tissue injury following ischemia-reperfusion in skeletal muscle.Microvasc. Res.199651327528710.1006/mvre.1996.0027 8992228
     [Google Scholar]
  106. AbouzakiN.A. ChristopherS. TrankleC. Inhibiting the inflammatory injury after myocardial ischemia reperfusion with plasma-derived alpha-1 antitrypsin: A post Hoc analysis of the VCU-α1RT study.J. Cardiovasc. Pharmacol.201871637537910.1097/FJC.0000000000000583 29634656
     [Google Scholar]
/content/journals/cvp/10.2174/0115701611345395241217053615
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Neutrophil Elastase as A Potential Target in Ischemia-reperfusion Injury
Curr. Vasc. Pharmacol. 23, 235 (2025); https://doi.org/10.2174/0115701611345395241217053615
/content/journals/cvp/10.2174/0115701611345395241217053615
/content/journals/cvp/10.2174/0115701611345395241217053615
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  • Article Type:     Review Article
Keyword(s): anti-inflammation; ischemia- reperfusion injury; myocardial infarction; Neutrophil elastase; preclinical research; sivelestat

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