{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:19Z","timestamp":1792785859250,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National key R & D","award":["2018YFA0107400"],"award-info":[{"award-number":["2018YFA0107400"]}]},{"name":"Programme for National Science Funds of China","award":["81600281"],"award-info":[{"award-number":["81600281"]}]},{"name":"Programme for National Science Funds of China","award":["81600310"],"award-info":[{"award-number":["81600310"]}]},{"name":"Programme for National Science Funds of China","award":["81730011"],"award-info":[{"award-number":["81730011"]}]},{"name":"Programme for National Science Funds of China","award":["81300078"],"award-info":[{"award-number":["81300078"]}]},{"name":"Programme for National Science Funds of China","award":["81800229"],"award-info":[{"award-number":["81800229"]}]},{"name":"Programme for Changjiang Scholars and Innovative Research Teamin University","award":["PCSIRT-14R08"],"award-info":[{"award-number":["PCSIRT-14R08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Either insufficient or excessive autophagy causes cellular death and contributes to myocardial ischaemia\/reperfusion (I\/R) injury. However, mechanisms controlling the \u2018right-level\u2019 of autophagy in the heart remains unidentified. Thioredoxin-interacting protein (TXNIP) is a pro-oxidative molecule knowing to contribute to I\/R injury. However, whether and how TXNIP may further inhibit suppressed autophagy or promote excessive cardiac autophagy in I\/R heart has not been previously investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Wild type or gene-manipulated adult male mice were subjected to myocardial I\/R. TXNIP was increased in myocardium during I\/R. Cardiac-specific TXNIP overexpression increased cardiomyocytes apoptosis and cardiac dysfunction, whereas cardiac-specific TXNIP knock-out significantly mitigated I\/R-induced apoptosis and improved cardiac function. Importantly, TXNIP overexpression significantly promoted cardiac autophagy and TXNIP knock-out significantly inhibited cardiac autophagy. In vitro studies demonstrated that TXNIP increased autophagosome formation but inhibited autophagosome clearance during myocardial reperfusion. Atg5 siRNA significantly decreased hypoxia\/reoxygenation induced apoptosis in cardiomyocytes with TXNIP overexpression. Mechanistically, TXNIP suppressed autophagosome clearance via increasing reactive oxygen species (ROS) level. However, TXNIP-increased autophagosome formation was not mediated by ROS as a ROS scavenger failed to block increased autophagosome formation in TXNIP overexpression heart. Finally, TXNIP directly interacted and stabilized Redd1 (an autophagy regulator), resulting in mTOR inhibition and autophagy activation. Redd1 knock-down significantly reduced autophagy formation and ameliorated I\/R injury in TXNIP overexpression hearts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results demonstrated that increased TXNIP-Redd1 expression is a novel signalling pathway that contributes to I\/R injury by exaggerating excessive autophagy during reperfusion. These observations advance our understanding of the mechanisms of myocardial I\/R injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvz152","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T09:12:44Z","timestamp":1561453964000},"page":"645-657","source":"Crossref","is-referenced-by-count":126,"title":["TXNIP\/Redd1 signalling and excessive autophagy: a novel mechanism of myocardial ischaemia\/reperfusion injury in mice"],"prefix":"10.1093","volume":"116","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 127 West Changle Rd, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-9709","authenticated-orcid":false,"given":"Rutao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Xijing Hospital, Fourth Military Medical 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