{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:47:14Z","timestamp":1785775634336,"version":"3.56.0"},"reference-count":71,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273922"],"award-info":[{"award-number":["82273922"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Endoplasmic reticulum (ER) stress can induce inflammation in heart failure (HF) by\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010adrenoceptor overactivation. In turn, inflammation can trigger ER stress. Cleaved caspase 3 produced during ER stress could induce apoptosis. Gasdermin E (GSDME), when activated by cleaved caspase 3, could induce pyroptosis. We have investigated the role of GSDME in\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010adrenoceptor overactivation\u2010induced cardiac injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Isoprenaline (ISO) was used to induce\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010adrenoceptor overactivation in mice and cultured myocardial cells. PERK inhibitor GSK2606414,\n                      <jats:italic>si\u2010Gsdme<\/jats:italic>\n                      and\n                      <jats:italic>Gsdme<\/jats:italic>\n                      deficiency mice were used to understand the relationship between ER stress and GSDME\u2010mediated pyroptosis\/inflammation under\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010adrenoceptor overactivation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      The protein levels of cleaved caspase 3 and GSDME\u2010N were increased in cardiac tissues in mice by isoprenaline, while\n                      <jats:italic>Gsdme<\/jats:italic>\n                      knockout inhibited inflammation and cardiac injury. KEGG enrichment analysis indicated that the role of GSDME was potentially associated with ER stress.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , inhibiting PERK\u2010mediated ER stress reduced cleaved caspase 3 and GSDME\u2010N expression and prevented pyroptosis induced by\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010adrenoceptor overactivation. Interestingly, knockdown of\n                      <jats:italic>Gsdme<\/jats:italic>\n                      not only prevented pyroptosis and inhibited inflammation but also down\u2010regulated cleaved caspase 3. Finally, either\n                      <jats:italic>Gsdme<\/jats:italic>\n                      knockdown\n                      <jats:italic>in vitro<\/jats:italic>\n                      or\n                      <jats:italic>Gsdme<\/jats:italic>\n                      deficiency\n                      <jats:italic>in vivo<\/jats:italic>\n                      suppressed PERK\u2010driven ER stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>GSDME functioned both downstream of cleaved caspase 3 to induce pyroptosis\/inflammation and upstream of caspase3 to increase caspasen 3 cleavage by enhancing ER stress, suggesting that GSDME was a key molecule to amplify ER stress and inflammation and might play an essential role in the development of HF. GSDME represents a potential pharmacological target for HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70516","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:21:07Z","timestamp":1780384867000},"page":"5245-5264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activated gasdermin E (GSDME) amplifies endoplasmic reticulum stress and inflammation in\n                    <i>\u03b2<\/i>\n                    \u2010adrenoceptor overactivation\u2010induced cardiac injury"],"prefix":"10.1111","volume":"183","author":[{"given":"Qi\u2010rui","family":"Shen","sequence":"first","affiliation":[{"name":"Central Laboratory, Shanghai Skin Disease Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang\u2010fang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, 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