{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:18:41Z","timestamp":1793305121006,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700384"],"award-info":[{"award-number":["81700384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2021,7,23]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>Pyroptosis is a morphologically and mechanistically distinct form of cell death and is characterized by GSDMD (gasdermin D) or GSDME (gasdermin E)-mediated necrosis with excessive inflammatory factor release. Cardiomyocyte necrosis and inflammation play key roles in the pathophysiology of myocardial ischemia\/reperfusion (I\/R) injury. However, whether cardiomyocytes undergo pyroptosis and the underlying mechanism in myocardial I\/R injury remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We aimed to investigate the role of pyroptosis in myocardial I\/R injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>In vivo and in vitro experiments were used to investigate pyroptosis of cardiomyocyte and the associated mechanisms during I\/R injury. Wild-type, Myh6-Cre, and cardiomyocyte-specific GSDMD-deficient male mice were subjected to I\/R. Human peripheral blood samples were collected from patients with acute ST-segment\u2013elevation myocardial infarction or control patients at 0, 1, and 24 hours after percutaneous coronary intervention in our department. The serum levels of GSDMD were measured by ELISA. Hypoxia\/reoxygenation induced cardiomyocyte pyroptosis and the release of mature IL (interleukin)-18 but not IL-1\u03b2, which mechanistically resulted from GSDMD cleavage by caspase-11 in cardiomyocytes. Furthermore, GSDMD gene deletion blocked hypoxia\/reoxygenation-induced cardiomyocyte pyroptosis and IL-18 release. GSDMD and its pyroptosis-inducing N-terminal fragment were upregulated in myocardial tissues after I\/R injury. Immunofluorescence analysis showed that GSDMD was mainly localized in cardiomyocytes. GSDMD deficiency in cardiomyocytes significantly reduced the I\/R-induced myocardial infarct size. Moreover, increased GSDMD serum levels were detected in patients exhibiting I\/R injury 1 hour after percutaneous coronary intervention for ST-segment\u2013elevation myocardial infarction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our results show that GSDMD-mediated cardiomyocyte pyroptosis is a key event during myocardial I\/R injury and that the caspase-11\/GSDMD pathway may be essential to this process. Additionally, GSDMD inhibition significantly reduces cardiomyocyte pyroptosis and I\/R-induced myocardial injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.120.318629","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T05:00:42Z","timestamp":1621573242000},"page":"383-396","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":333,"title":["GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I\/R Injury"],"prefix":"10.1161","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0805-3759","authenticated-orcid":true,"given":"Huairui","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China (H.S., Y.G., Z.D., J.Y., X.L., S.Z., L.M., F.Z., K.H., A.S., J.G.)."},{"name":"NHC Key Laboratory of Viral Heart Diseases, Shanghai, China 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