Correlation of low-density lipoprotein modification by myeloperoxidase with hypochlorous acid formation

Myeloperoxidase is an enzyme in phagocytes which catalyzes several redox re actions. A major product is hypochlorous acid which appears to be important in inflammatory processes such as atherosclerosis. The aim of this study w as to investigate whether the kinetics of low-density lipoprotein modificat ion by the myeloperoxidase/hydrogen peroxide/chloride system in vitro confo rm to the established kinetics of hypochlorous acid formation and to compar e 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. Vari ation of the concentration of low-density lipoprotein, hydrogen peroxide, a nd 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 incre ases caused inhibition of low-density lipoprotein modification. The inhibit ory effect of higher low-density lipoprotein concentrations might be releva nt, since these concentrations occur in the human aortic intima. Furthermor e, a positive correlation was found between the maximal rate of low-density lipoprotein modification and the acidity of the medium. In summary, low-de nsity lipoprotein modification is affected by the myeloperoxidase/hydrogen peroxide/chloride system in a similar manner to hypochlorous acid productio n. We conclude that myeloperoxidase, which has been detected in atheroscler otic lesions, is able to modify low-density lipoprotein into the form which is taken up by macrophages in an uncontrolled manner.