{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:47:38Z","timestamp":1790138858335,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["04151816"],"award-info":[{"award-number":["04151816"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ischemic heart disease is a leading cause of morbidity and mortality. Repressor activator protein 1 (Rap1), an established telomere\u2010associated protein, is a novel modulator of hypoxia\u2010induced apoptosis. This study aimed to explore the potential direct role of Rap1 in myocardial ischemia\/reperfusion injury (I\/RI) and to determine the underlying molecular mechanism. In a mouse model of myocardial I\/RI (30\u2010min of left descending coronary artery ligation followed by 2\u2010h reperfusion), Rap1 deficiency significantly reduced myocardial infarct size (IS) and improved cardiac systolic\/diastolic function. This was associated with a reduction in apoptosis in the post\u2010ischemic myocardium. In H9C2 and primary cardiomyocytes, Rap1 knockdown or knockout significantly suppressed hypoxia\/reoxygenation (H\/R)\u2010induced cell injury and apoptosis through increasing the phosphorylation\/activation of STAT3 at site Ser\n                    <jats:sup>727<\/jats:sup>\n                    and translocation of STAT3 to the nucleus. We surmise this since Stattic (selective STAT3 inhibitor) pretreatment canceled the abovementioned protective effect. Furthermore, co\u2010immunoprecipitation assay revealed a direct interaction between Rap1 and STAT3, but not JAK2, suggesting that the association of Rap1 with STAT3 may contribute to the reduced activity of STAT3 (Ser\n                    <jats:sup>727<\/jats:sup>\n                    ) upon H\/R stimulation. In conclusion, Rap1 deficiency protects the heart from ischemic damage through STAT3\u2010dependent reduction of cardiomyocyte apoptosis, which may yield viable target for pharmacological intervention in ischemic heart disease.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901592rr","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T03:37:38Z","timestamp":1580873858000},"page":"4482-4496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Deletion of Rap1 protects against myocardial ischemia\/reperfusion injury through suppressing cell apoptosis via activation of STAT3 signaling"],"prefix":"10.1096","volume":"34","author":[{"given":"Yin","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology The University of Hong Kong Hong Kong SAR 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