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CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis

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...

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Autores principales: Wang, Ling-Fang, Li, Qian, Wen, Ke, Zhao, Qi-Hang, Zhang, Ya-Ting, Zhao, Jia-Le, Ding, Qi, Guan, Xiao-Hui, Xiao, Yun-Fei, Deng, Ke-Yu, Xin, Hong-Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650707/
https://www.ncbi.nlm.nih.gov/pubmed/37958991
http://dx.doi.org/10.3390/ijms242116008
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author Wang, Ling-Fang
Li, Qian
Wen, Ke
Zhao, Qi-Hang
Zhang, Ya-Ting
Zhao, Jia-Le
Ding, Qi
Guan, Xiao-Hui
Xiao, Yun-Fei
Deng, Ke-Yu
Xin, Hong-Bo
author_facet Wang, Ling-Fang
Li, Qian
Wen, Ke
Zhao, Qi-Hang
Zhang, Ya-Ting
Zhao, Jia-Le
Ding, Qi
Guan, Xiao-Hui
Xiao, Yun-Fei
Deng, Ke-Yu
Xin, Hong-Bo
author_sort Wang, Ling-Fang
collection PubMed
description 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.
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spelling pubmed-106507072023-11-06 CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis Wang, Ling-Fang Li, Qian Wen, Ke Zhao, Qi-Hang Zhang, Ya-Ting Zhao, Jia-Le Ding, Qi Guan, Xiao-Hui Xiao, Yun-Fei Deng, Ke-Yu Xin, Hong-Bo Int J Mol Sci Article 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. MDPI 2023-11-06 /pmc/articles/PMC10650707/ /pubmed/37958991 http://dx.doi.org/10.3390/ijms242116008 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Ling-Fang
Li, Qian
Wen, Ke
Zhao, Qi-Hang
Zhang, Ya-Ting
Zhao, Jia-Le
Ding, Qi
Guan, Xiao-Hui
Xiao, Yun-Fei
Deng, Ke-Yu
Xin, Hong-Bo
CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis
title CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis
title_full CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis
title_fullStr CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis
title_full_unstemmed CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis
title_short CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis
title_sort cd38 deficiency alleviates diabetic cardiomyopathy by coordinately inhibiting pyroptosis and apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650707/
https://www.ncbi.nlm.nih.gov/pubmed/37958991
http://dx.doi.org/10.3390/ijms242116008
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