ArticleBiomolecules & biomedicine2023
Exogenous spermidine alleviates diabetic cardiomyopathy via suppressing reactive oxygen species, endoplasmic reticulum stress, and Pannexin-1-mediated ferroptosis.
Article in Biomolecules & biomedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 17 citations in OpenAlex.
- Implications of ferritinophagy in cardiovascular diseases and its pharmacological modulation: underlying mechanisms and clinical translation strategies.Cellular & molecular biology letters · 2026Review
- Empagliflozin Ameliorates Diabetic Cardiomyopathy by Inhibiting Ferroptosis via SIRT3: Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Article
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- Decellularized Extracellular Matrix/Gellan Gum Hydrogels Enriched with Spermine for Cardiac Models.Gels (Basel, Switzerland) · 2026Article
- Pannexins in the heart: cell-specific expression and contributions to disease.Cell and tissue research · 2026Review
- Mitochondrial Dysfunction in Type 2 Diabetes and Metabolic Syndrome: Mechanisms, Biomarkers, and Emerging Therapies.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Pannexins in the vasculature.American journal of physiology. Heart and circulatory physiology · 2025Review
- Oxidative stress and ferroptosis in diabetic cardiomyopathy: mechanistic interplay and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2025Review
- Ferroptosis in Cardiovascular Diseases and Ferroptosis-Related Intervention Approaches.Cardiovascular drugs and therapy · 2025Review
- Obesity accelerates cardiovascular ageing.European heart journal · 2025Review
- Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.Acta pharmaceutica Sinica. B · 2025Article
- Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Ferroptosis: mechanism and role in diabetes-related cardiovascular diseases.Cardiovascular diabetology · 2025Review
- EGCG attenuated spinal cord injury by inhibiting ferroptosis via activation of HMOX1 expression and suppression of HIF-1 signaling pathway.Iranian journal of basic medical sciences · 2025Article
- Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis.International journal of molecular sciences · 2024Review
- Diabetic Cardiomyopathy and Cell Death: Focus on Metal-Mediated Cell Death.Cardiovascular toxicology · 2024Review
- Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury.International journal of molecular sciences · 2024Review
- Ferroptosis in diabetic cardiomyopathy: from its mechanisms to therapeutic strategies.Frontiers in endocrinology · 2024Review
- Polyamines: their significance for maintaining health and contributing to diseases.Cell communication and signaling : CCS · 2023Review
- Exogenous Spermidine Alleviates Diabetic Myocardial Fibrosis Via Suppressing Inflammation and Pyroptosis in db/db MiceBalkan medical journal · 2023Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine (SPD) has cardioprotective effects. Here, we verified the hypothesis of SPD's protective effects on DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of SPD. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated in the myocardium of db/db mice, respectively. We found that diabetic mice showed cardiac dysfunction in 12 weeks. Conversely, exogenous SPD could improve cardiac functions and reduce the deposition of collagens, myocardial damage, reactive oxygen species (ROS) levels, and endoplasmic reticulum stress (ERS) in diabetic mouse hearts. Our results also demonstrated that cardiomyocytes displayed ferroptosis and then activated Pannexin-1 expression, which resulted in the increase of the extracellular adenosine triphosphate (ATP). Subsequently, increased ATP as a paracrine molecule combined to purinergic receptor P2X7 to activate ERK1/2 signaling pathway in cardiomyocytes and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, SPD could reverse these molecular processes. Our findings indicate an important new mechanism for DCM and suggest that SPD has potential applicability to protect against deterioration of cardiac function with DCM.
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