Oxidative Modification of Lipoproteins in Cardiovascular Pathophysiology

The oxidative modification of circulating lipoproteins, notably low-density lipoprotein (LDL), is now recognised as a central event in the initiation and progression of atherosclerotic cardiovascular disease. Under conditions of elevated reactive oxygen species (ROS) or metal-catalysed redox reactions, polyunsaturated lipids within the lipoprotein particle undergo peroxidation to generate lipid hydroperoxides and reactive aldehydes such as malondialdehyde. These oxidised moieties covalently modify apolipoprotein components, transforming native LDL into a pro-inflammatory form that is avidly taken up by macrophage scavenger receptors. Accumulation of lipid-laden macrophages leads to foam cell formation and the development of fatty streaks in the arterial intima. Concurrent depletion of intrinsic antioxidants such as vitamin E and impairment of enzyme systems including paraoxonase-1 exacerbate lipoprotein susceptibility to oxidation. Beyond LDL, high-density lipoprotein (HDL) also undergoes oxidative alterations that impair its anti-atherogenic functions, including reverse cholesterol transport and endothelial protection. The interplay between oxidised lipoproteins, endothelial dysfunction and inflammatory mediators underpins plaque evolution, destabilisation and clinical events such as myocardial infarction and stroke. Emerging evidence highlights that modulation of lipoprotein oxidative status through pharmacological agents, dietary antioxidants or lifestyle interventions holds promise for novel therapeutic and preventive strategies with global relevance.

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Oxidative Modification of Lipoproteins in Cardiovascular Pathophysiology publication trend

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Technical terms

Low-density lipoprotein (LDL): A plasma particle rich in cholesterol and apolipoprotein B that delivers cholesterol to peripheral tissues and is prone to oxidative modification.

Oxidised LDL (oxLDL): LDL that has undergone lipid peroxidation and apolipoprotein alteration, rendering it pro-inflammatory and atherogenic.

Reactive oxygen species (ROS): Highly reactive molecules such as superoxide and hydroxyl radicals that drive lipid peroxidation.

Paraoxonase-1 (PON1): A serum enzyme associated with HDL that hydrolyses oxidised lipids and protects against lipoprotein oxidation.

Foam cell: A lipid-laden macrophage in the arterial wall that arises from uptake of modified lipoproteins and contributes to plaque formation.

References

1. Lipid Oxidation Products and the Risk of Cardiovascular Diseases: Role of Lipoprotein Transport. Antioxidants (2024).
2. Metformin Impedes Oxidation of LDL In Vitro. Pharmaceutics (2023).
3. Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease. European Journal of Medical Research (2023).