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Circular RNAs (circRNAs) play important roles in cardiac pathophysiology. However, the role of circRNAs in response to exercise training and biological mechanisms responsible for exercise-induced cardiac protection remain largely unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>RNA sequencing was used to profile circRNA expression in adult mouse cardiomyocytes that were isolated from mice with or without exercise training. Exercise-induced circRNA circUtrn was significantly increased in swimming-trained adult mouse cardiomyocytes. In vivo, circUtrn was found to be required for exercise-induced physiological cardiac hypertrophy. circUtrn inhibition abolished the protective effects of exercise on myocardial ischaemia\u2013reperfusion remodelling. circUtrn overexpression prevented myocardial ischaemia\u2013reperfusion-induced acute injury and pathological cardiac remodelling. In vitro, overexpression of circUtrn promoted H9 human embryonic stem cell\u2013induced cardiomyocyte growth and survival via protein phosphatase 5 (PP5). Mechanistically, circUtrn directly bound to PP5 and regulated the stability of PP5 in a ubiquitin\u2013proteasome-dependent manner. Hypoxia-inducible factor 1\u03b1\u2013dependent splicing factor SF3B1 acted as an upstream regulator of circUtrn in cardiomyocytes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The circRNA circUtrn is upregulated upon exercise training in the heart. Overexpression of circUtrn can prevent myocardial I\/R-induced injury and pathological cardiac remodelling.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad161","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T14:58:44Z","timestamp":1698505124000},"page":"2638-2652","source":"Crossref","is-referenced-by-count":53,"title":["Exercise-induced circular RNA circUtrn is required for cardiac physiological hypertrophy and prevents myocardial ischaemia\u2013reperfusion injury"],"prefix":"10.1093","volume":"119","author":[{"given":"Lijun","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University (The Sixth People\u2019s Hospital of Nantong), School of Life Science, Shanghai University , 881 Yonghe Road, Chongchuan District, Nantong 226011 , China"},{"name":"Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research 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