{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:51:24Z","timestamp":1789692684529,"version":"4.0.1"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"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 Institute of Health","award":["RO1HL134366"],"award-info":[{"award-number":["RO1HL134366"]}]},{"name":"National Institute of Health","award":["R01HL133167"],"award-info":[{"award-number":["R01HL133167"]}]},{"name":"National Institute of Health","award":["R01HL142281"],"award-info":[{"award-number":["R01HL142281"]}]},{"name":"Value and Efficiency Teaching and Research"},{"name":"Virginia Commonwealth University School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Deregulation of mTOR (mammalian target of rapamycin) signalling occurs in diabetes, which exacerbates injury following myocardial infarction (MI). We therefore investigated the infarct-limiting effect of chronic treatment with rapamycin (RAPA, mTOR inhibitor) in diabetic mice following myocardial ischaemia\/reperfusion (I\/R) injury and delineated the potential protective mechanism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Adult male diabetic (db\/db) or wild-type (WT) (C57) mice were treated with RAPA (0.25\u2009mg\/kg\/day, intraperitoneal) or vehicle (5% DMSO) for 28\u2009days. The hearts from treated mice were subjected to global I\/R in Langendorff mode. Cardiomyocytes, isolated from treated mice, were subjected to simulated ischaemia\/reoxygenation (SI\/RO) to assess necrosis and apoptosis. Myocardial infarct size was increased in diabetic heart following I\/R as compared to WT. Likewise, enhanced necrosis and apoptosis were observed in isolated cardiomyocytes of diabetic mice following SI\/RO. Treatment with RAPA reduced infarct size as well as cardiomyocyte necrosis and apoptosis of diabetes and WT mice. RAPA increased STAT3 phosphorylation and miRNA-17\/20a expression in diabetic hearts. In addition, RAPA restored AKT phosphorylation (target of mTORC2) but suppressed S6 phosphorylation (target of mTORC1) following I\/R injury. RAPA-induced cardioprotection against I\/R injury as well as the induction of miR-17\/20a and AKT phosphorylation were abolished in cardiac-specific STAT3-deficient diabetic mice, without alteration of S6 phosphorylation. The infarct-limiting effect of RAPA was obliterated in cardiac-specific miRNA-17-92-deficient diabetic mice. The post-I\/R restoration of phosphorylation of STAT3 and AKT with RAPA were also abolished in miRNA-17-92-deficient diabetic mice. Additionally, RAPA suppressed the pro-apoptotic prolyl hydroxylase (Egln3\/PHD3), a target of miRNA-17\/20a in diabetic hearts, which was abrogated in miRNA-17-92-deficient diabetic mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Induction of STAT3-miRNA-17-92 signalling axis plays a critical role in attenuating MI in RAPA-treated diabetic mice. Our study indicates that chronic treatment with RAPA might be a promising pharmacological intervention for attenuating MI and improving prognosis in diabetic patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz315","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T20:09:44Z","timestamp":1573848584000},"page":"2103-2115","source":"Crossref","is-referenced-by-count":26,"title":["STAT3-miR-17\/20 signalling axis plays a critical role in attenuating myocardial infarction following rapamycin treatment in diabetic mice"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-2553","authenticated-orcid":false,"given":"Arun","family":"Samidurai","sequence":"first","affiliation":[{"name":"Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean K","family":"Roh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6381-3776","authenticated-orcid":false,"given":"Meeta","family":"Prakash","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-8456","authenticated-orcid":false,"given":"David","family":"Durrant","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi N","family":"Salloum","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh C","family":"Kukreja","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7020B, Richmond, VA 23298-0204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-7277","authenticated-orcid":false,"given":"Anindita","family":"Das","sequence":"additional","affiliation":[{"name":"Division of 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