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

作     者：Panat Yanpiset Chayodom Maneechote Sirawit Sriwichaiin Natthaphat Siri-Angkul Siriporn C.Chattipakorn Nipon Chattipakorn 

作者机构：Cardiac Electrophysiology Research and Training CenterFaculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Cardiac Electrophysiology UnitDepartment of PhysiologyFaculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai UniversityChiang Mai 50200Thailand Department of Oral Biology and Diagnostic SciencesFaculty of DentistryChiang Mai UniversityChiang Mai 50200Thailand 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2023年第13卷第1期

页      面：29-53页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学] 

基　　金：supported by the NSTDA Research Chair grant from the National Science and Technology Development Agency Thailand(NC) the Senior Research Scholar Grant from the National Research Council of Thailand(SCC) the Chiang Mai University Center of Excellence Award(NC) the National Research Council of Thailand,Fundamental Fund 2022,Chiang Mai University(FF65/044)(CM) the National Research Council of Thailand(NRCT)(N42A650187)(CM)。 

主　　题：Pyroptosis Gasdermin D Heart Ischemia Ischemia-reperfusion injury Myocardial infarction 

摘      要：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.