Myeloperoxidase, a heme protein secreted by activated phagocytes, is present and enzymatically active in human atherosclerotic lesions. In the current studies, we explored the possibility that reactive nitrogen species generated by myeloperoxidase promote lipid peroxidation of low density lipoprotein (LDL)^a modification that may render the lipoprotein atherogenic. We found that myeloperoxidase, an H 2 O 2 -generating system and nitrite (NO 3 2 ) peroxidized LDL lipids. The process required NO 3 2 and each component of the enzymatic system; it was inhibited by catalase, cyanide and ascorbate, a potent scavenger of aqueous phase radicals. LDL peroxidation did not require chloride ion, and it was little affected by the hypochlorous acid scavenger taurine. Collectively, these results suggest that lipid peroxidation is promoted by a nitrogen dioxide radical-like species. These observations indicate that myeloperoxidase, by virtue of its ability to form reactive nitrogen intermediates, may promote lipid peroxidation and atherogenesis.z 1999 Federation of European Biochemical Societies.

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The aim of the study was to demonstrate an activation of polymorpho-nuclear leukocytes (PMNs) in chronic progressive atherosclerosis (ATH). A group of patients with ATH, and a group of ATH patients under aspirin (ASA) therapy were compared with control persons without atherosclerotic alterations (healthy controls). Each group comprised 15 male age-matched subjects. The following inflammatory parameters related to PMN activities were measured: the polymorphonuclear leukocyte (PMN) blood count; blood PMN migration and reactive oxygen species release in vitro; the blood levels of PMN elastase, malondialdehyde, antibodies to oxidized LDL and soluble ICAM-1. In ATH patients, the PMN blood counts and the share of blood PMNs migrating upon platelet activating factor and leukotriene B4 stimulation were significnatly above the values of the healthy controls, while the other parameters were not significantly altered. ASA treatment attenuated the inflammatory response and reduced the differences between ATH and the healthy controls. It can be concluded that, in patients with chronic progressive atherosclerosis, PMNs are involved in the inflammatory process underlying the disease.

The ability of ceruloplasmin (Cp) to oxidize lowdensity lipoproteins (LDL) in the presence of water-soluble antioxidants was investigated and a reaction mechanism proposed. Ascorbate strongly enhanced LDL oxidation, but only after its rapid consumption. Dehydroascorbate enhanced Cpmediated LDL oxidation even more strongly. Lipid-soluble antioxidants and water-soluble peroxides did not show noticeable activation. However, loading of LDL with lipid hydroperoxides increased the initial oxidation rate. We conclude that Cp mediates a localized redox cycle, where reduction of Cp-Cu 2+ is effected by water-soluble reductants and reoxidation by liposoluble hydroperoxides. ß