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Gasdermin D-mediated pyroptosis in myocardial ischemia and reperfusion injury:Cumulative evidence for future cardioprotective strategies

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Acta Pharmaceutica Sinica B 2023年第1期13卷 29-53页

作者： Panat Yanpiset chayodom maneechote Sirawit Sriwichaiin Natthaphat Siri-Angkul Siriporn C.Chattipakorn Nipon Chattipakorn Cardiac Electrophysiology Research and Training Center Faculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Cardiac Electrophysiology Unit Department of PhysiologyFaculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Center of Excellence in Cardiac Electrophysiology Research Chiang Mai UniversityChiang Mai 50200Thailand Department of Oral Biology and Diagnostic Sciences Faculty of DentistryChiang Mai UniversityChiang Mai 50200Thailand

Cardiomyocyte death is one of the major mechanisms contributing to the development of myocardial infarction(MI)and myocardial ischemia/reperfusion(MI/R)injury.Due to the limited regenerative ability of cardiomyocytes,understanding the mechanisms of cardiomyocyte death is necessary.Pyroptosis,one of the regulated programmed cell death pathways,has recently been shown to play important roles in MI and MI/R injury.Pyroptosis is activated by damage-associated molecular patterns(DAMPs)that are released from damaged myocardial cells and activate the formation of an apoptosisassociated speck-like protein containing a CARD(ASC)interacting with NACHT,LRR,and PYD domains-containing protein 3(NLRP3),resulting in caspase-1 cleavage which promotes the activation of Gasdermin D(GSDMD).This pathway is known as the canonical pathway.GSDMD has also been shown to be activated in a non-canonical pathway during MI and MI/R injury via caspase-4/5/11.Suppression of GSDMD has been shown to provide cardioprotection against MI and MI/R injury.Although the effects of MI or MI/R injury on pyroptosis have previously been discussed,knowledge concerning the roles of GSDMD in these settings remains limited.In this review,the evidence from in vitro,in vivo,and clinical studies focusing on cardiac GSDMD activation during MI and MI/R injury is comprehensively summarized and discussed.Implications from this review will help pave the way for a new therapeutic target in ischemic heart disease.

关键词： Pyroptosis Gasdermin D Heart Ischemia Ischemia-reperfusion injury Myocardial infarction

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