Vitamin E oxidation in human atherosclerotic lesions

Area of Science:

• Biochemistry
• Cardiovascular Science
• Nutritional Science

Background:

• Low-density lipoprotein (LDL) oxidation is central to atherosclerosis development.
• Vitamin E (alpha-tocopherol, TOH) is investigated for its potential anti-atherogenic properties.
• The specific pathways and extent of TOH oxidation in atherosclerotic lesions are not well understood.

Purpose of the Study:

• To investigate the types and extent of alpha-tocopherol (TOH) oxidation and its relationship to lipid oxidation in human atherosclerotic lesions.
• To identify the primary oxidants responsible for TOH oxidation in the artery wall.
• To inform the development of antioxidant strategies for preventing atherosclerosis.

Main Methods:

• Gas chromatography-mass spectrometry was used to analyze oxidized lipids and TOH oxidation products (TQ, epoxy-TQ) in human atherosclerotic lesions.
• In vitro oxidation of LDL was performed with various oxidants (radical and non-radical) to establish TOH oxidation product profiles.
• Lesions were analyzed across different stages of atherosclerosis.

Main Results:

• In vitro, radical oxidants produced predominantly tocopherylquinone epoxides, while non-radical oxidants like hypochlorite yielded more alpha-tocopherylquinone (TQ).
• In human lesions, TQ was the major TOH oxidation product, comprising <20% of total TOH, regardless of disease stage.
• TOH oxidation was highest in early lesions, exceeding lipid oxidation, while oxidized lipid increased with lesion severity.

Conclusions:

• Two-electron oxidants, rather than radical species, appear to be the primary drivers of TOH oxidation in the artery wall.
• While TOH oxidation is limited, it is a significant process occurring alongside substantial lipid oxidation in atherogenesis.
• These findings have implications for the design of antioxidant supplements targeting LDL oxidation and atherosclerosis prevention.