Sequential change in physicochemical properties of LDL during oxidative modification

Area of Science:

• Cardiovascular Biology
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Oxidized low-density lipoprotein (LDL) is a key factor in atherosclerosis.
• The precise structural and physicochemical changes during LDL oxidation remain incompletely understood.
• This knowledge gap hinders mechanistic understanding of LDL's atherogenic potential.

Purpose of the Study:

• To investigate time-dependent alterations in the chemical composition and physical properties of LDL during oxidation.
• To elucidate the structural basis of LDL's atherogenicity.

Main Methods:

• LDL oxidation was induced using human embryonic endothelial cells and copper ions.
• Time-course analysis of chemical composition (lipids, proteins) and physical properties (density, diameter) was performed.
• Changes in glycerolipids, phospholipids, and apolipoprotein B (apoB) were monitored.

Main Results:

• Oxidation led to glycerolipid hydrolysis, decreasing triglyceride and choline-phospholipid while increasing lysophosphatidylcholine.
• Apolipoprotein B fragmentation occurred, though overall protein content remained.
• LDL particle density increased (d ≥ 1.044) within 10 hours.
• LDL particle diameter initially decreased then increased, with a rise in discoidal particles.

Conclusions:

• Oxidative degradation of core lipids and increased surface lysophosphatidylcholine contribute to LDL remodeling.
• These dynamic structural changes provide a mechanistic basis for the atherogenicity of oxidized LDL.
• Understanding these transformations is crucial for developing targeted therapies for atherosclerosis.