Myeloperoxidase and hypochlorite, but not copper ions, oxidize heparin-bound LDL particles and release them from heparin.
A key factor in atherosclerosis is the retention of low density lipoprotein (LDL) in the extracellular matrix of the arterial intima, where it binds to the negatively charged glycosaminoglycan chains of proteoglycans. Oxidation may lead to modification of the lysine residues of apolipoprotein B-100 of LDL, which normally mediate the binding of LDL to glycosaminoglycans. Here, we studied whether various modes of oxidation can release LDL from heparin, a glycosaminoglycan with a strong negative charge, in vitro. We found that copper ions were unable to oxidize heparin-bound LDL particles because of their redox inactivation by the glycosaminoglycans. In contrast, myeloperoxidase and hypochlorite, a product of myeloperoxidase, were able to oxidize heparin-bound LDL, and this oxidation led to the release of the oxidized particles from heparin. When the released LDL particles were compared with the residual heparin-bound LDL particles, the released particles were more electronegative and contained more modified lysine residues than did the particles that remained bound. Because human atherosclerotic lesions contain catalytically active myeloperoxidase and (lipo)proteins modified by hypochlorite, the results suggest that myeloperoxidase-secreting monocytes/macrophages in the arterial intima can oxidize and extract LDL from the extracellular matrix with ensuing uptake by the macrophages of the oxidized and released LDL, with eventual formation of foam cells.
Pentikäinen
M O
MO
Wihuri Research Institute, Helsinki, Finland.
Oörni
K
K
Kovanen
P T
PT
D001011:Aorta; D003300:Copper / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism*
D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D006997:Hypochlorous Acid; D003300:Copper; D006493:Heparin; D009195:Peroxidase