Abstract：
Regular exercise training benefits cardiovascular health and effectively reduces the risk for cardiovascular disease. 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.
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-reperfusion remodelling. circUtrn overexpression prevented myocardial ischaemia-reperfusion-induced acute injury and pathological cardiac remodelling. In vitro, overexpression of circUtrn promoted H9 human embryonic stem cell-induced cardiomyocyte growth and survival via protein phosphatase 5 (PP5). Mechanistically, circUtrn directly bound to PP5 and regulated the stability of PP5 in a ubiquitin-proteasome-dependent manner. Hypoxia-inducible factor 1α-dependent splicing factor SF3B1 acted as an upstream regulator of circUtrn in cardiomyocytes.
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.
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-reperfusion remodelling. circUtrn overexpression prevented myocardial ischaemia-reperfusion-induced acute injury and pathological cardiac remodelling. In vitro, overexpression of circUtrn promoted H9 human embryonic stem cell-induced cardiomyocyte growth and survival via protein phosphatase 5 (PP5). Mechanistically, circUtrn directly bound to PP5 and regulated the stability of PP5 in a ubiquitin-proteasome-dependent manner. Hypoxia-inducible factor 1α-dependent splicing factor SF3B1 acted as an upstream regulator of circUtrn in cardiomyocytes.
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.
摘要：
目的：定期运动训练有益于心血管健康，有效降低心血管疾病风险。环状RNA（circularRNAs）在心脏病理生理学中起重要作用。然而,circRNAs在运动训练反应中的作用和负责运动诱导的心脏保护的生物学机制仍在很大程度上未知.
结果：RNA测序用于分析成年小鼠心肌细胞中的circRNA表达，这些心肌细胞是从有或没有运动训练的小鼠中分离的。在游泳训练的成年小鼠心肌细胞中，运动诱导的circRNA-cirUtrn显着增加。在体内,发现circUtrn是运动引起的生理性心脏肥大所必需的。CircUtrn抑制消除了运动对心肌缺血/再灌注重塑的保护作用。CircUtrn过表达可预防心肌缺血/再灌注引起的急性损伤和病理性心脏重塑。体外，circUtrn的过表达通过蛋白磷酸酶PP5促进H9人胚胎干细胞诱导的心肌细胞生长和存活。机械上,circUtrn直接结合PP5并以泛素-蛋白酶体依赖性方式调节PP5的稳定性。缺氧诱导因子1α依赖性剪接因子SF3B1在心肌细胞中充当cirUtrn的上游调节因子。
结论：circRNACircUtrn在心脏运动训练后上调。circUtrn的过表达可以预防I/R引起的心肌损伤和病理性心脏重塑。
■CircRNAcirUtrn是运动诱发的生理性心脏肥大发展所必需的。CircUtrn抑制消除了运动对I/R重塑的保护作用。此外，circUtrn过表达可预防心肌I/R诱导的急性损伤和病理性心脏重塑。我们的发现表明，circUtrn升高及其对I/R损伤的保护作用可能在I/R损伤和病理性心脏重塑中具有治疗前景。
结果：RNA测序用于分析成年小鼠心肌细胞中的circRNA表达，这些心肌细胞是从有或没有运动训练的小鼠中分离的。在游泳训练的成年小鼠心肌细胞中，运动诱导的circRNA-cirUtrn显着增加。在体内,发现circUtrn是运动引起的生理性心脏肥大所必需的。CircUtrn抑制消除了运动对心肌缺血/再灌注重塑的保护作用。CircUtrn过表达可预防心肌缺血/再灌注引起的急性损伤和病理性心脏重塑。体外，circUtrn的过表达通过蛋白磷酸酶PP5促进H9人胚胎干细胞诱导的心肌细胞生长和存活。机械上,circUtrn直接结合PP5并以泛素-蛋白酶体依赖性方式调节PP5的稳定性。缺氧诱导因子1α依赖性剪接因子SF3B1在心肌细胞中充当cirUtrn的上游调节因子。
结论：circRNACircUtrn在心脏运动训练后上调。circUtrn的过表达可以预防I/R引起的心肌损伤和病理性心脏重塑。
■CircRNAcirUtrn是运动诱发的生理性心脏肥大发展所必需的。CircUtrn抑制消除了运动对I/R重塑的保护作用。此外，circUtrn过表达可预防心肌I/R诱导的急性损伤和病理性心脏重塑。我们的发现表明，circUtrn升高及其对I/R损伤的保护作用可能在I/R损伤和病理性心脏重塑中具有治疗前景。
