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Jiangxi Province","award":["20212BAB206087"],"award-info":[{"award-number":["20212BAB206087"]}]},{"name":"Natural Science Foundation of Jiangxi Province","award":["20212BDH81020"],"award-info":[{"award-number":["20212BDH81020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic cardiomyopathy is one of the diabetes mellitus-induced cardiovascular complications that can result in heart failure in severe cases, which is characterized by cardiomyocyte apoptosis, local inflammation, oxidative stress, and myocardial fibrosis. CD38, a main hydrolase of NAD+ in mammals, plays an important role in various cardiovascular diseases, according to our previous studies. However, the role of CD38 in diabetes-induced cardiomyopathy is still unknown. Here, we report that global deletion of the CD38 gene significantly prevented diabetic cardiomyopathy induced by high-fat diet plus streptozotocin (STZ) injection in CD38 knockout (CD38-KO) mice. We observed that CD38 expression was up-regulated, whereas the expression of Sirt3 was down-regulated in the hearts of diabetic mice. CD38 deficiency significantly promoted glucose metabolism and improved cardiac functions, exemplified by increased left ventricular ejection fraction and fractional shortening. In addition, we observed that CD38 deficiency markedly decreased diabetes or high glucose and palmitic acid (HG + PA)-induced pyroptosis and apoptosis in CD38 knockout hearts or cardiomyocytes, respectively. Furthermore, we found that the expression levels of Sirt3, mainly located in mitochondria, and its target gene FOXO3a were increased in CD38-deficient hearts and cardiomyocytes with CD38 knockdown under diabetic induction conditions. In conclusion, we demonstrated that CD38 deficiency protected mice from diabetes-induced diabetic cardiomyopathy by reducing pyroptosis and apoptosis via activating NAD+\/Sirt3\/FOXO3a signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms242116008","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T08:15:56Z","timestamp":1699258556000},"page":"16008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Ling-Fang","family":"Wang","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Hang","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Le","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ding","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Guan","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Fei","family":"Xiao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Yu","family":"Deng","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Bo","family":"Xin","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. 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