ISSN : 2146-3123
E-ISSN : 2146-3131

Exogenous Spermidine Alleviates Diabetic Myocardial Fibrosis Via Suppressing Inflammation and Pyroptosis in db/db Mice
Can Wei1,2, Jiyu Xu3, Yong Liu4, Javeria Qadir5, Shumin Zhang6, Hui Yuan1,6
1School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang, China
2Department of Pathophysiology, Harbin Medical University, Harbin, China
3School of Medical Imaging, Mudanjiang Medical University, Mudanjiang, China
4Animal Research Institute, Research Department, Mudanjiang Medical University, Mudanjiang, China
5Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
6School of Stomatology, Mudanjiang Medical University, Mudanjiang, China
DOI : 10.4274/balkanmedj.galenos.2023.2023-3-102
Pages : 333-343


Background: The main pathological feature of diabetic cardiomyopathy (DCM) caused by diabetes mellitus is myocardial fibrosis. According to recent studies in cardiology, it has been suggested that spermidine (SPD) has cardioprotective properties.
Aims: To explore the role and mechanism of SPD in alleviating myocardial fibrosis of DCM.
Study Design: In vivo and in vitro study.
Methods: Type 2 diabetic mice and primary neonatal mouse cardiac fibroblasts (CFs) were selected. Measurements of serum-related markers, echocardiographic analysis, and immunohistochemistry were used to evaluate myocardial fibrosis injury and the effects of SPD. The proliferation and migration of CFs undergoing different treatments were studied. Immunoblotting and real-time quantitative reverse transcription polymerase chain reaction were used to demonstrate molecular mechanisms.
Results: In vivo immunoblotting analysis indicated a downregulation of ornithine decarboxylase and an upregulation of SPD/spermine N1-acetyltransferase. We observed cardiac dysfunction in diabetic mice after 12 weeks. However, the administration of exogenous SPD improved cardiac function, decreased collagen deposition, and reduced myocardial tissue damage. mRNA expression levels of NLRP3, Caspase-1, GSDMD-N, interleukin (IL)-1β, IL-17A, and IL-18 were increased and suppressed in the myocardium of db/db mice upon treatment with SPD. SPD inhibited the proliferation, migration, and collagen secretion of high-glucose-treated fibroblasts in vitro. SPD inhibits the activation of the TGF-β1/Smad signaling pathway and decreases collagen deposition by reducing pyroptosis and Smad-7 ubiquitination levels.
Conclusion: Based on our findings, SPD may have potential applications in protecting against the deterioration of cardiac function in patients with DCM due to a significant new mechanism for diabetic myocardial fibrosis that we discovered.

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