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Iron-ascorbate-phospholipid mediated modification of low density lipoprotein
P Greenspan1, H Yu, R L Gutman
1Department of Pharmacology and Toxicology, School of Pharmacy, University of Georgia, Athens 30602, USA.
Biochimica Et Biophysica Acta
|June 11, 1996
Summary
Phosphatidylcholine oxidation, initiated by iron and ascorbate, modifies low-density lipoprotein (LDL). This oxidized LDL is then avidly metabolized by macrophages, contributing to atherosclerosis progression.
Area of Science:
- Biochemistry
- Cardiovascular Research
- Lipid Metabolism
Background:
- Low-density lipoprotein (LDL) oxidation is implicated in atherosclerosis.
- Previous research focused on direct LDL oxidation, neglecting other atheroma lipids.
- Oxidation of other lipids, like phospholipids, may contribute to LDL modification.
Purpose of the Study:
- To investigate the relationship between oxidized phospholipids and LDL modification.
- To determine if oxidized phospholipids mediate LDL susceptibility to macrophage uptake.
Main Methods:
- Incubation of phosphatidylcholine with ferrous sulfate and ascorbic acid.
- Measurement of thiobarbituric acid reactive substances (TBARS) to assess lipid peroxidation.
- Assessment of LDL electrophoretic mobility and macrophage metabolism.
- Inhibition studies using Probucol.
Main Results:
- Iron and ascorbate alone did not modify LDL.
- Phosphatidylcholine oxidation in the presence of iron and ascorbate generated TBARS.
- This process led to LDL modification, evidenced by increased electrophoretic mobility.
- Modified LDL showed significantly increased metabolism by macrophages.
- Probucol inhibited LDL modification.
Conclusions:
- Oxidized phosphatidylcholine, not direct LDL oxidation, mediates LDL modification.
- This mechanism highlights a novel pathway in atheroma development.
- Targeting phospholipid oxidation could be a therapeutic strategy for atherosclerosis.