Correlation of low-density lipoprotein modification by myeloperoxidase with hypochlorous acid formation.
Myeloperoxidase is an enzyme in phagocytes which catalyzes several redox reactions. A major product is hypochlorous acid which appears to be important in inflammatory processes such as atherosclerosis. The aim of this study was to investigate whether the kinetics of low-density lipoprotein modification by the myeloperoxidase/hydrogen peroxide/chloride system in vitro conform to the established kinetics of hypochlorous acid formation and to compare the results with known in vivo data. The absorbance at 234 nm was applied to study the kinetics of the modification of low-density lipoprotein. Variation of the concentration of low-density lipoprotein, hydrogen peroxide, and chloride, respectively, had a biphasic effect on the maximal rate of low-density lipoprotein modification. Increasing the substrates up to certain threshold levels resulted in increased modification, however, further increases caused inhibition of low-density lipoprotein modification. The inhibitory effect of higher low-density lipoprotein concentrations might be relevant, since these concentrations occur in the human aortic intima. Furthermore, a positive correlation was found between the maximal rate of low-density lipoprotein modification and the acidity of the medium. In summary, low-density lipoprotein modification is affected by the myeloperoxidase/hydrogen peroxide/chloride system in a similar manner to hypochlorous acid production. We conclude that myeloperoxidase, which has been detected in atherosclerotic lesions, is able to modify low-density lipoprotein into the form which is taken up by macrophages in an uncontrolled manner.
Jerlich
A
A
Institute of Biochemistry, University of Graz, Austria.
Horakova
L
L
Fabjan
J S
JS
Giessauf
A
A
Jürgens
G
G
Schaur
R J
RJ
D000328:Adult; D001161:Arteriosclerosis / Q000097:blood* / Q000201:enzymology*; D002712:Chlorides / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006997:Hypochlorous Acid / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism*
D002712:Chlorides; D008078:Cholesterol, LDL; D016877:Oxidants; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase