Ironing out the details: ferroptosis and its relevance to diabetic cardiomyopathy

Ferroptosis is a newly identified myocardial cell death mechanism driven by iron-dependent lipid peroxidation. The presence of elevated intramyocardial lipid levels and excessive iron in patients with diabetes suggest a predominant role of ferroptosis in diabetic cardiomyopathy. As myocardial cell d...

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Bibliographic Details
Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2023-12, Vol.325 (6), p.R665-R681
Main Authors: Gawargi, Flobater I, Mishra, Paras K
Format: Article
Language:English
Subjects:
Cardiomyopathy
Cell death
Cell Death - physiology
Congestive heart failure
Diabetes
Diabetes Mellitus
Diabetic Cardiomyopathies
Ferroptosis
Glutathione
Glutathione peroxidase
Heart Failure
Humans
Iron
Iron - metabolism
Lipid Peroxidation
Lipids
Molecular modelling
Mortality
Peroxidase
Peroxidation
Review
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Summary:Ferroptosis is a newly identified myocardial cell death mechanism driven by iron-dependent lipid peroxidation. The presence of elevated intramyocardial lipid levels and excessive iron in patients with diabetes suggest a predominant role of ferroptosis in diabetic cardiomyopathy. As myocardial cell death is a precursor of heart failure, and intensive glycemic control cannot abate the increased risk of heart failure in patients with diabetes, targeting myocardial cell death via ferroptosis is a promising therapeutic avenue to prevent and/or treat diabetic cardiomyopathy. This review provides updated and comprehensive molecular mechanisms underpinning ferroptosis, clarifies several misconceptions about ferroptosis, emphasizes the importance of ferroptosis in diabetes-induced myocardial cell death, and offers valuable approaches to evaluate and target ferroptosis in the diabetic heart. Furthermore, basic concepts and ideas presented in this review, including glutathione peroxidase-4-independent and mitochondrial mechanisms of ferroptosis, are also important for investigating ferroptosis in other diabetic organs, as well as nondiabetic and metabolically compromised hearts.
ISSN:0363-6119
1522-1490
1522-1490
DOI:10.1152/ajpregu.00117.2023