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This study was intended to explore the effect of Tregs on diabetic cardiomyopathy (DCM) using a <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Eight\u2010week\u2010old male <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice were randomly divided into four groups: the control group, administered 200\u2009\u03bcL phosphate\u2010buffered saline; the small\u2010dose Treg group, administered 10<jats:sup>5<\/jats:sup> Tregs; the large\u2010dose Treg group, administered 10<jats:sup>6<\/jats:sup> Tregs; and the PC group, administered 100\u2009\u03bcg anti\u2010CD25 specific antibody (PC61) and 10<jats:sup>6<\/jats:sup> Tregs. After 12\u2009weeks, mice were euthanized. Transthoracic echocardiography was carried out at the beginning and end of the experiment. Relevant basic experiments to evaluate the effects of Tregs on DCM were carried out.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Echocardiography showed that the impaired diastolic and systolic functions were significantly improved in mice administered large\u2010dose Tregs. Large\u2010dose Tregs significantly ameliorated myocardial hypertrophy and fibrosis, and decreased hypertrophic gene expression and collagen deposition. The protective effects of Tregs on diabetic hearts were associated with decreased oxidative stress, inflammatory response and apoptosis. In addition, Tregs promoted the activation of the phosphatidylinositol 3\u2010kinase\u2013protein kinase\u2009B signaling pathway, whereas they inhibited extracellular signal\u2010regulated kinase\u20091\/2 and Jun N\u2010terminal kinase phosphorylation, which might be responsible for the cardioprotective role of Tregs against DCM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tregs ameliorated myocardial hypertrophy and fibrosis, improved cardiac dysfunction, and protected against DCM progression in <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice. The mechanisms involved a decrease of inflammatory response, oxidative stress and apoptosis, which might be mediated by phosphatidylinositol 3\u2010kinase\u2013protein kinase\u2009B and mitogen\u2010activated protein kinase pathways. Hence, Tregs might serve as a promising therapeutic approach for DCM treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14251","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T16:58:23Z","timestamp":1719680303000},"page":"1191-1201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Regulatory T\u2009cells protect against diabetic cardiomyopathy in <i>db\/db<\/i> mice"],"prefix":"10.1111","volume":"15","author":[{"given":"Kai","family":"Zhang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ge","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Department of Cardiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Meng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Kong","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-9096","authenticated-orcid":false,"given":"Xiao","family":"Meng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan 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