Oxidative lipoprotein remodelling in atherogenesis: Mechanistic insights and therapeutic potential

Oxidative modification of lipoproteins, essentially the oxidised low-density lipoprotein (oxLDL), is increasingly recognised as a critical driver of atherogenesis beyond conventional lipid measures. While low-density lipoprotein cholesterol (LDL-c) remains central to cardiovascular risk assessment, accumulating evidence indicates that oxidative transformation of lipoproteins contributes directly to vascular inflammation, endothelial dysfunction, and plaque progression. This review synthesises molecular, biochemical, and genetic evidence linking oxidative lipoprotein remodelling to dyslipidaemia and atherogenic risk. Mechanistic insights highlight the roles of reactive oxygen species, inflammatory signalling pathways, and receptor-mediated uptake in driving oxLDL formation and downstream vascular injury. To complement the narrative evaluation of summarized evidence, a structured literature search identified 23 eligible clinical studies indicating that pharmacological, nutraceutical, dietary, and lifestyle strategies could modulate oxLDL through mechanistically distinct pathways. Interestingly, these effects are not consistently aligned with reductions in LDL-c, thus supporting a mechanistic dissociation between lipid burden and oxidative lipoprotein modification. In fact, emerging therapeutic approaches, including proprotein convertase subtilisin kexin9 (PCSK9) inhibition, icosapent ethyl, omega-3 fatty acids, nutraceutical antioxidants, and RNA-based strategies, show potential in targeting oxidative lipoprotein pathways, although their efficacy varies across biological and clinical contexts. Collectively, findings from this review position oxidative lipoprotein modification as a biologically relevant and potentially modifiable dimension of atherogenic risk, supporting its integration into future cardiovascular risk assessment and intervention strategies.