{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:08:21Z","timestamp":1756462101565,"version":"3.41.2"},"reference-count":137,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":350,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL118376-01","1R01HL138988-01A1"],"award-info":[{"award-number":["1R01HL118376-01","1R01HL138988-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Rapamycin (Rap), an inhibitor of mTORC1, reduces obesity and improves lifespan in mice. However, hyperglycemia and lipid disorders are adverse side effects in patients receiving Rap treatment. We previously reported that diabetes induces pansuppression of cardiac cytokines in Zucker obese rats (ZO\u2010C). Rap treatment (750\u2009<jats:italic>\u03bc<\/jats:italic>g\/kg\/day for 12 weeks) reduced their obesity and cardiac fibrosis significantly; however, it increased their hyperglycemia and did not improve their cardiac diastolic parameters. Moreover, Rap treatment of healthy Zucker lean rats (ZL\u2010C) induced cardiac fibrosis. Rap\u2010induced changes in ZL\u2010C\u2019s cardiac cytokine profile shared similarities with that of diabetes\u2010induced ZO\u2010C. Therefore, we hypothesized that the cardiac microRNA transcriptome induced by diabetes and Rap treatment could share similarities. Here, we compared the cardiac miRNA transcriptome of ZL\u2010C to ZO\u2010C, Rap\u2010treated ZL (ZL\u2010Rap), and ZO (ZO\u2010Rap). We report that 80% of diabetes\u2010induced miRNA transcriptome (40 differentially expressed miRNAs by minimum 1.5\u2010fold in ZO\u2010C versus ZL\u2010C; <jats:italic>p<\/jats:italic> \u2264 0.05) is similar to 47% of Rap\u2010induced miRNA transcriptome in ZL (68 differentially expressed miRNAs by minimum 1.5\u2010fold in ZL\u2010Rap versus ZL\u2010C; <jats:italic>p<\/jats:italic> \u2264 0.05). This remarkable similarity between diabetes\u2010induced and Rap\u2010induced cardiac microRNA transcriptome underscores the role of miRNAs in Rap\u2010induced insulin resistance. We also show that Rap treatment altered the expression of the same 17 miRNAs in ZL and ZO hearts indicating that these 17 miRNAs comprise a unique Rap\u2010induced cardiac miRNA signature. Interestingly, only four miRNAs were significantly differentially expressed between ZO\u2010C and ZO\u2010Rap, indicating that, unlike the nondiabetic heart, Rap did not substantially change the miRNA transcriptome in the diabetic heart. <jats:italic>In silico<\/jats:italic> analyses showed that (a) mRNA\u2010miRNA interactions exist between differentially expressed cardiac cytokines and miRNAs, (b) human orthologs of rat miRNAs that are strongly correlated with cardiac fibrosis may modulate profibrotic TGF\u2010<jats:italic>\u03b2<\/jats:italic> signaling, and (c) changes in miRNA transcriptome caused by diabetes or Rap treatment include cardioprotective miRNAs indicating a concurrent activation of an adaptive mechanism to protect the heart in conditions that exacerbate diabetes.<\/jats:p>","DOI":"10.1155\/2018\/8364608","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T23:42:40Z","timestamp":1545090160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparison of Cardiac miRNA Transcriptomes Induced by Diabetes and Rapamycin Treatment and Identification of a Rapamycin\u2010Associated Cardiac MicroRNA Signature"],"prefix":"10.1155","volume":"2018","author":[{"given":"Anthony M.","family":"Belenchia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhavi P.","family":"Gavini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan G.","family":"Toedebusch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent 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