CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis.
CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis.
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DOI：
10.3390/ijms242116008
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发表时间：
2023-11-06
影响因子：
5.6
通讯作者：
Xin HB
中科院分区：
文献类型：
--
作者：
Wang LF;Li Q;Wen K;Zhao QH;Zhang YT;Zhao JL;Ding Q;Guan XH;Xiao YF;Deng KY;Xin HB
糖尿病心肌病是糖尿病引起的心血管并发症之一，严重时可导致心力衰竭，其特点是心肌细胞凋亡、局部炎症、氧化应激和心肌纤维化。根据我们之前的研究，CD38是哺乳动物中NAD+的主要水解酶，在多种心血管疾病中发挥着重要作用。然而，CD38在糖尿病引起的心肌病中的作用仍不清楚。在此，我们报告，在 CD38 敲除 (CD38-KO) 小鼠中，CD38 基因的整体缺失显着预防了高脂饮食加链脲佐菌素 (STZ) 注射诱导的糖尿病心肌病。我们观察到糖尿病小鼠心脏中 CD38 表达上调，而 Sirt3 表达下调。 CD38 缺乏显着促进葡萄糖代谢并改善心脏功能，例如左心室射血分数和缩短分数增加。此外，我们观察到 CD38 缺乏可显着降低糖尿病或高葡萄糖和棕榈酸 (HG + PA) 诱导的 CD38 敲除心脏或心肌细胞的细胞焦亡和细胞凋亡。此外，我们发现在糖尿病诱导条件下，CD38缺陷的心脏和CD38敲低的心肌细胞中Sirt3（主要位于线粒体）及其靶基因FOXO3a的表达水平增加。总之，我们证明 CD38 缺陷通过激活 NAD+/Sirt3/FOXO3a 信号通路减少细胞焦亡和细胞凋亡，从而保护小鼠免受糖尿病诱发的糖尿病心肌病。
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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影响因子：
20.1
作者：
Oka SI;Byun J;Huang CY;Imai N;Ralda G;Zhai P;Xu X;Kashyap S;Warren JS;Alan Maschek J;Tippetts TS;Tong M;Venkatesh S;Ikeda Y;Mizushima W;Kashihara T;Sadoshima J
通讯作者：
Sadoshima J
CD38促进血管紧张素II诱导的心脏肥大
影响因子：
5.3
作者：
Guan XH;Hong X;Zhao N;Liu XH;Xiao YF;Chen TT;Deng LB;Wang XL;Wang JB;Ji GJ;Fu M;Deng KY;Xin HB
通讯作者：
Xin HB
DOI：
10.1161/circheartfailure.120.008170
发表时间：
2021-08
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Chiao YA;Chakraborty AD;Light CM;Tian R;Sadoshima J;Shi X;Gu H;Lee CF
通讯作者：
Lee CF
影响因子：
13.8
作者：
Chini EN;Chini CCS;Espindola Netto JM;de Oliveira GC;van Schooten W
通讯作者：
van Schooten W
CD38 缺乏通过激活 SIRT1/FOXO 介导的抗氧化应激途径保护心脏免受缺血/再灌注损伤。
影响因子：
--
作者：
Guan XH;Liu XH;Hong X;Zhao N;Xiao YF;Wang LF;Tang L;Jiang K;Qian YS;Deng KY;Ji G;Fu M;Xin HB
通讯作者：
Xin HB