Molecular signatures of lipid peroxidation in cardiomyopathy: unraveling oxidative mechanisms in cardiac cell dysfunction.

Cardiomyopathy, like other major cardiovascular diseases, is becoming increasingly prevalent and represents a growing public health challenge. Although both genetic and acquired factors contribute to its development, obesity and diabetes remain among the most significant modifiable risks. These conditions share key pathological features, including oxidative stress, inflammation, and elevated lipid peroxidation, all of which can disrupt cellular metabolism and function. Lipid oxidation products, irrespective of their origin, are characterized by increased oxygenation and hydrophilicity compared with their nonoxidized precursors. These properties confer high chemical reactivity toward cellular macromolecules, enabling the formation of covalent protein adducts that alter protein structure and function. Consequently, accumulation of excess lipid oxidation products initiates cytotoxic processes that disrupt mitochondrial homeostasis, potentially impairing cardiomyocyte function and contributing to broader cardiovascular pathology. Although lipid peroxidation frequently accompanies oxidative stress and inflammation, the mechanistic interrelationships among these processes in cardiomyopathy remain poorly defined. This narrative review synthesizes current evidence on the role of lipid peroxidation in cardiomyopathy, with particular emphasis on emerging insights into its interactions with oxidative stress and inflammatory pathways. Furthermore, it examines the impact of lipid oxidation products on mitochondrial dysfunction and cardiomyocyte viability, as well as their role in promoting cardiac fibroblast activation and myocardial fibrosis, all of which are key processes underlying the initiation and progression of cardiomyopathy.