Mixed lineage kinase 3 contributes to myocardial ischemia/reperfusion injury by regulating neutrophil activation

Abbate A, Dinarello CA (2015) Anti-inflammatory therapies in acute coronary syndromes: is IL-1 blockade a solution? Eur Heart J 36:337–339. https://doi.org/10.1093/eurheartj/ehu369

Article  PubMed  Google Scholar 

Ballesteros I, Rubio-Ponce A, Genua M, Lusito E, Kwok I, Fernández-Calvo G, Khoyratty TE, van Grinsven E, González-Hernández S, Nicolás-Ávila JÁ, Vicanolo T, Maccataio A, Benguría A, Li JL, Adrover JM, Aroca-Crevillen A, Quintana JA, Martín-Salamanca S, Mayo F, Ascher S, Barbiera G, Soehnlein O, Gunzer M, Ginhoux F, Sánchez-Cabo F, Nistal-Villán E, Schulz C, Dopazo A, Reinhardt C, Udalova IA, Ng LG, Ostuni R, Hidalgo A (2020) Co-option of neutrophil fates by tissue environments. Cell. https://doi.org/10.1016/j.cell.2020.10.003

Article  PubMed  Google Scholar 

Bartels M, Govers AM, Fleskens V, Lourenço AR, Pals CE, Vervoort SJ, van Gent R, Brenkman AB, Bierings MB, Ackerman SJ, van Loosdregt J, Coffer PJ (2015) Acetylation of C/EBPε is a prerequisite for terminal neutrophil differentiation. Blood 125:1782–1792. https://doi.org/10.1182/blood-2013-12-543850

Article  CAS  PubMed  Google Scholar 

Burn GL, Foti A, Marsman G, Patel DF, Zychlinsky A (2021) The neutrophil. Immunity 54:1377–1391. https://doi.org/10.1016/j.immuni.2021.06.006

Article  CAS  PubMed  Google Scholar 

Calamaras TD, Pande S, Baumgartner RA, Kim SK, McCarthy JC, Martin GL, Tam K, McLaughlin AL, Wang G-R, Aronovitz MJ, Lin W, Aguirre JI, Baca P, Liu P, Richards DA, Davis RJ, Karas RH, Jaffe IZ, Blanton RM (2021) MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms. JCI Insight. https://doi.org/10.1172/jci.insight.149075

Article  PubMed  PubMed Central  Google Scholar 

Chamilos G, Gregorio J, Meller S, Lande R, Kontoyiannis DP, Modlin RL, Gilliet M (2012) Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 120:3699–3707. https://doi.org/10.1182/blood-2012-01-401364

Article  CAS  PubMed  PubMed Central  Google Scholar 

Döring Y, Drechsler M, Wantha S, Kemmerich K, Lievens D, Vijayan S, Gallo RL, Weber C, Soehnlein O (2012) Lack of neutrophil-derived CRAMP reduces atherosclerosis in mice. Circ Res 110:1052–1056. https://doi.org/10.1161/circresaha.112.265868

Article  PubMed  Google Scholar 

Evrard M, Kwok IWH, Chong SZ, Teng KWW, Becht E, Chen J, Sieow JL, Penny HL, Ching GC, Devi S, Adrover JM, Li JLY, Liong KH, Tan L, Poon Z, Foo S, Chua JW, Su IH, Balabanian K, Bachelerie F, Biswas SK, Larbi A, Hwang WYK, Madan V, Koeffler HP, Wong SC, Newell EW, Hidalgo A, Ginhoux F, Ng LG (2018) Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions. Immunity 48:364-379.e368. https://doi.org/10.1016/j.immuni.2018.02.002

Article  CAS  PubMed  Google Scholar 

Franchi L, Eigenbrod T, Núñez G (2009) Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol 183:792–796. https://doi.org/10.4049/jimmunol.0900173

Article  CAS  PubMed  Google Scholar 

Frangogiannis NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11:255–265. https://doi.org/10.1038/nrcardio.2014.28

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gadang V, Kohli R, Myronovych A, Hui DY, Perez-Tilve D, Jaeschke A (2013) MLK3 promotes metabolic dysfunction induced by saturated fatty acid-enriched diet. Am J Physiol Endocrinol Metab 305:E549–E556. https://doi.org/10.1152/ajpendo.00197.2013

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gadang V, Konaniah E, Hui DY, Jaeschke A (2014) Mixed-lineage kinase 3 deficiency promotes neointima formation through increased activation of the RhoA pathway in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 34:1429–1436. https://doi.org/10.1161/ATVBAHA.114.303439

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gallo KA, Johnson GL (2002) Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol 3:663–672

Article  CAS  PubMed  Google Scholar 

Goodfellow VS, Loweth CJ, Ravula SB, Wiemann T, Nguyen T, Xu Y, Todd DE, Sheppard D, Pollack S, Polesskaya O, Marker DF, Dewhurst S, Gelbard HA (2013) Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem 56:8032–8048. https://doi.org/10.1021/jm401094t

Article  CAS  PubMed  PubMed Central  Google Scholar 

He S, Liu S, Wu X, Xin M, Ding S, Xin D, Ouyang H, Zhang J (2016) Protective role of downregulated MLK3 in myocardial adaptation to chronic hypoxia. J Physiol Biochem 73:371–380. https://doi.org/10.1007/s13105-017-0561-5

Article  CAS  PubMed  Google Scholar 

Heusch G (2013) Cardioprotection: chances and challenges of its translation to the clinic. Lancet 381:166–175. https://doi.org/10.1016/S0140-6736(12)60916-7

Article  PubMed  Google Scholar 

Heusch G (2020) Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol 17:773–789. https://doi.org/10.1038/s41569-020-0403-y

Article  PubMed  Google Scholar 

Heusch G (2024) Myocardial ischemia/reperfusion: translational pathophysiology of ischemic heart disease. Med 5:10–31. https://doi.org/10.1016/j.medj.2023.12.007

Article  CAS  PubMed  Google Scholar 

Horckmans M, Ring L, Duchene J, Santovito D, Schloss MJ, Drechsler M, Weber C, Soehnlein O, Steffens S (2017) Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J 38:187–197. https://doi.org/10.1093/eurheartj/ehw002

Article  CAS  PubMed  Google Scholar 

Hu S, Zhang F, Wang J, Zhang J, Li C, Lyu Y, Wang Y, Huang R, Gao Y, Yang H, Qian J, Tang W, Cao J, Ge J (2025) MMP9(High) neutrophils are critical mediators of neutrophil extracellular traps formation and myocardial ischemia/reperfusion injury. Adv Sci 12:e2415205. https://doi.org/10.1002/advs.202415205

Article  CAS  Google Scholar 

Hu S, Zhang F, Wang J, Zhang J, Li C, Lyu Y, Wang Y, Huang R, Gao Y, Yang H, Qian J, Tang W, Cao J, Ge J (2025) MMP9High neutrophils are critical mediators of neutrophil extracellular traps formation and myocardial ischemia/reperfusion injury. Adv Sci. https://doi.org/10.1002/advs.202415205

Article  Google Scholar 

Huang S, Frangogiannis NG (2018) Anti-inflammatory therapies in myocardial infarction: failures, hopes and challenges. Br J Pharmacol 175:1377–1400. https://doi.org/10.1111/bph.14155

Article  CAS  PubMed  PubMed Central  Google Scholar 

Investigators P (2007) Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease. Neurology 69:1480–1490. https://doi.org/10.1212/01.wnl.0000277648.63931.c0

Article  CAS  Google Scholar 

Köhler D, Leiss V, Beichert L, Killinger S, Grothe D, Kushwaha R, Schröter A, Roslan A, Eggstein C, Focken J, Granja T, Devanathan V, Schittek B, Lukowski R, Weigelin B, Rosenberger P, Nürnberg B, Beer-Hammer S (2024) Targeting Gαi2 in neutrophils protects from myocardial ischemia reperfusion injury. Basic Res Cardiol 119:717–732. https://doi.org/10.1007/s00395-024-01057-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kurotaki D, Yamamoto M, Nishiyama A, Uno K, Ban T, Ichino M, Sasaki H, Matsunaga S, Yoshinari M, Ryo A, Nakazawa M, Ozato K, Tamura T (2014) IRF8 inhibits C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils. Nat Commun 5:4978. https://doi.org/10.1038/ncomms5978

Article  CAS  PubMed  Google Scholar 

Lau A, Rahn JJ, Chappellaz M, Chung H, Benediktsson H, Bihan D, von Mässenhausen A, Linkermann A, Jenne CN, Robbins SM, Senger DL, Lewis IA, Chun J, Muruve DA (2022) Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury. Sci Adv 8:eabm0142. https://doi.org/10.1126/sciadv.abm0142

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leung IW

Comments (0)

No login
gif