{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T07:17:06Z","timestamp":1783667826133,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2024YFA1802202"],"award-info":[{"award-number":["2024YFA1802202"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170278"],"award-info":[{"award-number":["82170278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204380"],"award-info":[{"award-number":["82204380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370242"],"award-info":[{"award-number":["82370242"]}],"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"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Surgical ventricular reconstruction (SVR) partially reverses left ventricular remodelling in postinfarction heart failure, yet residual cardiac dysfunction persists through unknown mechanisms. We investigated ferroptosis involvement in post\u2010SVR pathology and explored pharmacological interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Myocardial infarction (MI) was induced in C57BL\/6 mice followed by SVR at 4\u00a0weeks. Cardiac function was assessed by echocardiography and pressure\u2013volume catheterization. Ferroptosis biomarkers were quantified. Connectivity Map analysis identified candidate compounds validated in Erastin\u2010challenged AC16 cardiomyocytes and SVR mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Compared with MI group, SVR improved the left ventricular end\u2010diastolic volume index by 36.8% but showed persistent iron overload, glutathione depletion and elevated malondialdehyde. Transcriptomic analysis identified 90 ferroptosis\u2010related differentially expressed genes following SVR. Connectivity Map prioritized three ferroptosis inhibitors, and chenodeoxycholic acid (CDCA) exhibited superior efficacy. Farnesoid X receptor (FXR) knockdown in AC16 cardiomyocytes exacerbated erastin\u2010induced ferroptosis, while CDCA co\u2010treatment significantly reduced erastin\u2010induced ROS production, upregulated glutathione peroxidase 4 (GPX4) expression, and restored superoxide dismutase activity, rescued the ferroptotic phenotype and reversed associated molecular changes in FXR\u2010knockdown cells. In SVR\u2010treated mice, 3\u2010week CDCA administration (50\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7day\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) reduced myocardial iron deposition by 14.8%, improved left ventricular ejection fraction from 23.73% to 31.61% and restored GSH\/GSSG ratio from 1.645 to 1.988. CDCA up\u2010regulated GPX4 expression by 1.573\u2010fold compared with the vehicle group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>SVR paradoxically exacerbates ferroptosis in residual myocardium through iron dysregulation and antioxidant depletion. CDCA, a primary bile acid activating FXR signalling, is a novel pharmacological strategy to mitigate post\u2010SVR ferroptosis and improve cardiac outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70542","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:49:41Z","timestamp":1783666181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting ferroptosis with chenodeoxycholic acid improves residual cardiac dysfunction after surgical ventricular reconstruction"],"prefix":"10.1111","author":[{"given":"Qiuhan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial Key Lab of Cardiac Function and Microcirculation Nanfang Hospital, Southern Medical University  Guangzhou China"},{"name":"Chongqing Hospital, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Chongqing 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Cardiology Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial Key Lab of Cardiac Function and Microcirculation Nanfang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial Key Lab of Cardiac Function and Microcirculation Nanfang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial Key Lab of Cardiac Function and Microcirculation Nanfang Hospital, Southern Medical University  Guangzhou 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