Human native, enzymatically modified and oxidized low density lipoproteins show different lipidomic pattern

Area of Science:

• Lipidomics
• Atherosclerosis Research
• Biochemistry

Background:

• Low-density lipoprotein (LDL) modifications are central to atherogenesis.
• Understanding diverse LDL modifications is crucial for elucidating their cellular effects.
• Lipidomic analysis provides a detailed molecular profile of LDL.

Purpose of the Study:

• To perform a comparative lipidomic analysis of distinct LDL modifications.
• To differentiate the lipid profiles of oxidized LDL (oxLDL) and enzymatically modified LDL (eLDL).
• To correlate lipidomic changes with potential cellular effects of modified LDL.

Main Methods:

• Comparative lipidomic analysis of native LDL, oxLDL (copper, HOCl, mmLDL, LipoxLDL), and eLDL.
• Quantification of lipid classes including free cholesterol (FC), cholesteryl esters (CE), phosphatidylcholine (PC), and lysophosphatidylcholine (LPC).
• Assessment of lipid alterations resulting from different oxidation and enzymatic modification methods.

Main Results:

• Enzymatic modification significantly decreased the cholesteryl ester proportion in LDL.
• Oxidized LDL exhibited reduced free cholesterol and cholesteryl esters due to conversion to oxysterols.
• Oxidized LDL showed a decrease in polyunsaturated phosphatidylcholine and a rise in lysophosphatidylcholine, effects less pronounced in eLDL.
• Mild oxidation (HOCl, lipoxygenase) did not significantly alter analyzed lipid classes.

Conclusions:

• Distinct lipidomic profiles characterize different LDL modifications.
• Oxidized LDL undergoes more profound lipid compositional changes than enzymatically modified LDL.
• Lipidomic characterization aids in understanding the diverse cellular consequences of modified LDL particles.