Cu(2+)-induced lipid oxidation in plasma: questionable relation between cholesterol oxidation and LDL modification

Area of Science:

• Biochemistry
• Cardiovascular Science
• Lipid Metabolism

Background:

• Oxidized low-density lipoproteins (LDL) are implicated in arterial cholesterol deposition.
• Oxysterols, cytotoxic products of cholesterol oxidation, may contribute to this process.
• Previous studies primarily used purified LDL, limiting in vivo relevance.

Purpose of the Study:

• To investigate the oxidation process of LDL within whole plasma.
• To determine the stage of oxysterol formation during LDL oxidation.
• To compare LDL oxidation in plasma with oxidation by endothelial cells.

Main Methods:

• Whole human plasma was subjected to copper-induced oxidation.
• Low-density lipoproteins (LDL) were isolated and analyzed for modifications.
• Changes in LDL density and oxysterol formation were monitored over time.

Main Results:

• Oxidation of the LDL ring structure, leading to oxysterol formation, was observed only after polyunsaturated fatty acids were largely depleted.
• Copper-induced oxidation of LDL in whole plasma resulted in a hydrated LDL density similar to that observed during endothelial cell-mediated oxidation.
• The LDL ring structure remained unmodified under conditions where polyunsaturated fatty acids were depleted.

Conclusions:

• Oxysterol formation occurs late in the LDL oxidation cascade within whole plasma.
• Copper-induced LDL oxidation in plasma mimics certain aspects of endothelial cell-mediated oxidation regarding LDL density.
• The timing of oxysterol formation suggests a distinct mechanism compared to early-stage LDL modifications.