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Oxidation of low density lipoprotein by iron or copper at acidic pH
1Rheumatology Section, Veterans Administration Hospital, San Diego, CA 92161, USA.
Insights
Acidic conditions accelerate the oxidation of low-density lipoprotein (LDL) by iron and copper, increasing its uptake by macrophages. This pH-dependent oxidation may explain LDL oxidation in atherosclerotic lesions.
Area of Science:
- Biochemistry
- Cardiovascular Science
Background:
- Oxidized low-density lipoprotein (LDL) is implicated in atherosclerosis.
- The influence of pH on LDL oxidation requires further investigation.
Purpose of the Study:
- To investigate the effect of pH on LDL oxidation induced by iron or copper.
- To determine the impact of pH on LDL oxidation products and macrophage uptake.
Main Methods:
- LDL oxidation was induced using iron or copper in the presence of cysteine.
- Experiments were conducted in Hanks' balanced salt solution (HBSS) and Ham's F-10 medium at varying pH levels.
- Oxidation products (hydroperoxides, TBARS, conjugated dienes) and macrophage uptake were measured.
Main Results:
- Acidic pH significantly decreased the lag phase and increased the rate of LDL oxidation by iron, enhancing macrophage uptake.
- Acidic pH increased the lag phase but ultimately promoted LDL oxidation by copper, also increasing macrophage uptake.
- Cysteine inhibited copper-induced LDL modification at both neutral and acidic pH.
Conclusions:
- Acidic pH promotes LDL oxidation, particularly in the presence of iron and cysteine.
- The findings suggest that localized acidic environments in atherosclerotic lesions may drive LDL oxidation.
- Understanding pH-dependent LDL oxidation is crucial for atherosclerosis research.
Abstract:
Oxidized low density lipoprotein (LDL) may play a significant role in atherosclerosis. We have investigated the effect of pH on the oxidation of LDL by iron or copper. When LDL was oxidized by iron in the presence of cysteine in either Hanks' balanced salt solution (HBSS) or Ham's F-10 medium, an acidic pH greatly decreased the lag period and increased the rate of formation of hydroperoxides and thiobarbituric acid-reactive substances (TBARS), and increased its uptake by macrophages. There was a dose-dependent increase of LDL oxidation at acidic pH in the presence of increasing concentrations of cysteine. When LDL was oxidized by copper in HBSS, an acidic pH increased the lag phase before the rapid formation of conjugated dienes, hydroperoxides, and TBARS, but increased its uptake by macrophages. Similar results were obtained using Ham's F-10 medium. Cysteine (100 microM) inhibited the modification of LDL by copper in HBSS at both pH 7.4 and 5.5 As atherosclerotic lesions may be acidic, these observations may help to explain why LDL oxidation occurs locally at these sites.