Myeloperoxidase-mediated oxidation of high-density lipoproteins: fingerprints of newly recognized potential proatherogenic lipoproteins.
Substantial evidence supports the notion that oxidative processes participate in the pathogenesis of atherosclerotic heart disease. Major evidence for myeloperoxidase (MPO) as enzymatic catalyst for oxidative modification of lipoproteins in the artery wall has been suggested in numerous studies performed with low-density lipoprotein. In contrast to low-density lipoprotein, plasma levels of high-density lipoprotein (HDL)-cholesterol and apoAI, the major apolipoprotein of HDL, inversely correlate with the risk of developing coronary artery disease. These antiatherosclerotic effects are attributed mainly to HDL's capacity to transport excess cholesterol from arterial wall cells to the liver during 'reverse cholesterol transport'. There is now strong evidence that HDL is a selective in vivo target for MPO-catalyzed oxidation impairing the cardioprotective and antiinflammatory capacity of this antiatherogenic lipoprotein. MPO is enzymatically active in human lesion material and was found to be associated with HDL extracted from human atheroma. MPO-catalyzed oxidation products are highly enriched in circulating HDL from individuals with cardiovascular disease where MPO concentrations are also increased. The oxidative potential of MPO involves an array of intermediate-generated reactive oxygen and reactive nitrogen species and the ability of MPO to generate chlorinating oxidants-in particular hypochlorous acid/hypochlorite-under physiological conditions is a unique and defining activity for this enzyme. All these MPO-generated reactive products may affect structure and function of HDL as well as the activity of HDL-associated enzymes involved in conversion and remodeling of the lipoprotein particle, and represent clinically useful markers for atherosclerosis.
Malle
Ernst
E
Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, A-8010 Graz, Austria. ernst.malle@meduni-graz.at
Marsche
Gunther
G
Panzenboeck
Ute
U
Sattler
Wolfgang
W
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010449:Peptide Mapping; D009195:Peroxidase / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008075:Lipoproteins, HDL; D009195:Peroxidase