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Review
. 2025 Jun 15;16(6):104665.
doi: 10.4239/wjd.v16.i6.104665.

Ferroptosis: A novel therapeutic target for diabetic cardiomyopathy

Gui-Zhi Li  1 , Jia-Yin Liu  2 , Hong Zhou  3
Affiliations
Review

Ferroptosis: A novel therapeutic target for diabetic cardiomyopathy

Gui-Zhi Li et al. World J Diabetes. .

Abstract

Ferroptosis is a new type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, and it plays a role in the occurrence and progression of diverse diseases. Diabetic cardiomyopathy (DCM), a serious cardiovascular complication in patients with diabetes, eventually progresses to refractory heart failure (HF), which increases the risk of hospitalization for HF and cardiovascular death in patients with diabetes. Despite glycemic control, effective strategies to prevent DCM onset are currently lacking. Accumulating evidence suggests that ferroptosis is involved in oxidative stress, inflammation, and abnormal autophagy in diabetic myocardium, which plays an important role in myocardial apoptosis, hypertrophy, and cardiac fibrosis. The inhibition of ferroptosis can relieve DCM. Presently, ferroptosis inhibitors have been broadly suggested for the treatment of iron overload-related cardiomyopathy. This article reviewed relevant studies to offer a new therapeutic target for DCM.

Keywords: Autophagy; Diabetic cardiomyopathy; Ferroptosis; Inflammation; Oxidative stress.

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Conflict of interest statement

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Figures

Figure 1
Figure 1
The primary signaling pathways and key regulatory factors of ferroptosis. TF: Transferrin; TFR1: Transferrin receptor1; DMT1: Divalent 311 metal transporter 1; ACSL4: Acyl-CoA synthetase long-chain family member 4; LPCAT3: Lysophosphatidylcholine acyltransferase 3; LOX: Lipoxygenase; SLC3A2: Solute carrier family 3 member 2; SLC7A11: Solute carrier family 7 member 11; GCL: Glutamate cysteine ligase; GSS: Glutathione synthase; Cys: Cystine; Glu: Glutamate; Gly: Glycine; NADPH: Nicotinamide adenine dinucleotide phosphate; ROS: Reactive oxygen species; PUFA: Polyunsaturated fatty acid; PUFA-PL: Polyunsaturated fatty acid-phospholipid; GPX4: Glutathione peroxidase; GSH: Glutathione.
Figure 2
Figure 2
Pathophysiological mechanism of diabetic cardiomyopathy. AGEs: Advanced glycation end products; RAAS: Renin-angiotensin-aldosterone system; DCM: Diabetic cardiomyopathy.
Figure 3
Figure 3
The regulatory role of ferroptosis in diabetic cardiomyopathy. Nrf2: Nuclear factor erythroid 2-related factor 2; SLC40A1: Solute carrier family 40 member 1; NCOA4: Nuclear receptor coactivator 4; TF: Transferrin; TFR1: Transferrin receptor1; DMT1: Divalent 311 metal transporter 1; ACSL4: Acyl-CoA synthetase long-chain family member 4; LPCAT3: Lysophosphatidylcholine acyltransferase 3; LOX: Lipoxygenase; SLC3A2: Solute carrier family 3 member 2; SLC7A11: Solute carrier family 7 member 11; GCL: Glutamate cysteine ligase; GSS: Glutathione synthase; Cys: Cystine; Glu: Glutamate; Gly: Glycine; ROS: Reactive oxygen species; PUFA: Polyunsaturated fatty acid; PUFA-PL: Polyunsaturated fatty acid-phospholipid; GPX4: Glutathione peroxidase; GSH: Glutathione; ARE: Antioxidant response elements.
See this image and copyright information in PMC

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