Ferroptosis in Diabetic Cardiomyopathy and Atherosclerosis: Mechanisms and Clinical Prospects

TL;DR

This review explains how ferroptosis, a type of cell death, contributes to heart and blood vessel diseases in diabetes and explores potential treatments.

Contribution

The paper provides a comprehensive analysis of ferroptosis mechanisms and therapies in diabetic cardiomyopathy and atherosclerosis.

Findings

Ferroptosis is linked to metabolic dysregulation in iron, lipids, and amino acids in cardiometabolic diseases.

Targeting ferroptosis with iron chelators and antioxidants shows therapeutic potential in reducing oxidative stress and inflammation.

Cell-specific ferroptosis mechanisms drive myocardial dysfunction and plaque instability in diabetic conditions.

Abstract

Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in the pathogenesis of cardiometabolic diseases (CMDs), particularly diabetic cardiomyopathy (DCM) and atherosclerosis (AS). This review comprehensively explores the metabolic pathways underlying ferroptosis, including dysregulation of iron, lipid, amino acid, and glucose metabolism, as well as involvement of the mevalonate pathway and key regulators such as NRF2 and p53. We analyze the cell type-specific mechanisms through which ferroptosis contributes to DCM and AS, driving myocardial dysfunction, plaque instability, and inflammatory amplification. Furthermore, we discuss emerging therapeutic strategies targeting ferroptosis, such as iron chelators, antioxidants, lipoxygenase inhibitors, ACSL4 inhibitors, nitroxides, and selenium supplements, which demonstrate potential in mitigating oxidative stress, restoring iron homeostasis, and suppressing inflammation. This review underscores the clinical relevance of targeting ferroptosis and highlights its promise as a novel therapeutic avenue for treating cardiometabolic diseases.

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