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Myeloperoxidase binds to low-density lipoprotein: potential implications for atherosclerosis
A C Carr1, M C Myzak, R Stocker
1Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331-6512, USA. anitra.carr@orst.edu
Abstract:
Myeloperoxidase (MPO), an abundant heme enzyme released by activated phagocytes, catalyzes the formation of a number of reactive species that can modify low-density lipoprotein (LDL) to a form that converts macrophages into lipid-laden or 'foam' cells, the hallmark of atherosclerotic lesions. Since MPO has been shown to bind to a number of different cell types, we investigated binding of MPO to LDL. Using the precipitation reagents phosphotungstate or isopropanol, MPO co-precipitated with LDL, retaining its catalytic activity. The association of MPO with LDL was confirmed using native gel electrophoresis. MPO was also found to co-precipitate with apolipoprotein B-100-containing lipoproteins in whole plasma. No precipitation of MPO was observed in lipoprotein-deficient plasma, and there was a dose-dependent increase in precipitation following addition of LDL to lipoprotein-deficient plasma. Binding of MPO to LDL could potentially enhance site-directed oxidation of the lipoprotein and limit scavenging of reactive oxygen species by antioxidants.
Insights
Myeloperoxidase (MPO) binds to low-density lipoprotein (LDL), potentially promoting atherosclerosis. This interaction may enhance LDL oxidation and hinder antioxidant activity, contributing to foam cell formation.
Area of Science:
- Biochemistry
- Cardiovascular Research
- Cell Biology
Background:
- Myeloperoxidase (MPO) is an enzyme released by phagocytes.
- MPO modifies low-density lipoprotein (LDL), leading to foam cell formation, a key feature of atherosclerosis.
- MPO's interaction with various cell types is known, but its binding to LDL was uninvestigated.
Purpose of the Study:
- To investigate the binding of Myeloperoxidase (MPO) to low-density lipoprotein (LDL).
- To understand the implications of MPO-LDL interaction in the context of atherosclerosis.
Main Methods:
- Co-precipitation of MPO and LDL using phosphotungstate or isopropanol.
- Confirmation of MPO-LDL association via native gel electrophoresis.
- Analysis of MPO precipitation with lipoproteins in whole plasma and lipoprotein-deficient plasma.
Main Results:
- MPO co-precipitated with LDL, retaining its catalytic activity.
- MPO associated with apolipoprotein B-100-containing lipoproteins in plasma.
- LDL addition to lipoprotein-deficient plasma showed a dose-dependent increase in MPO precipitation.
Conclusions:
- Myeloperoxidase (MPO) directly binds to low-density lipoprotein (LDL).
- This binding may enhance site-directed oxidation of LDL.
- The MPO-LDL interaction could potentially limit antioxidant scavenging of reactive oxygen species, promoting atherosclerotic lesion development.