Myeloperoxidase (MPO),In contrast to low density lipoproteins (LDL), 1 high plasma concentrations of high density lipoproteins (HDL) are associated with a decreased risk for the development of coronary artery disease, an effect commonly attributed to their central role in reverse cholesterol transport (1). During this process, HDL is able to promote efflux of cholesterol from peripheral tissues, and the accepted cholesterol is (at least in part) esterified by the action of lecithin-cholesterol acyltransferase (2). Cholesteryl esters (CEs) formed by the lecithin-cholesterol acyltransferase reaction are then transferred from HDL to other lipoproteins mediated by the cholesterol ester transfer protein or are delivered to the liver for bilary secretion or reutilization during lipoprotein assembling (3).Within the oxidative theory, HDL appears to be Janus-faced (4 -6). The majority of lipid hydroperoxides (the first detectable products of lipoprotein oxidation) in plasma are transported in the HDL fraction (7), and HDL was suggested to act as a sink for preformed lipid hydro(pero)xides. HDL-associated cholesteryl ester hydroperoxides, which are probably transferred to HDL by the action of the cholesterol ester transfer protein (8), are preferentially catabolized over nonoxidized CEs; this was shown in HepG2 cells (9), in situ perfused rat liver (10), and intact rats (11). HDL was also shown to protect LDL from lipid peroxidation, inhibiting the formation of lipid hydroperoxides but not the formation of conjugated dienes (12). On the other hand, HDL is more easily oxidized than LDL (7), HDLassociated lecithin-cholesterol acyltransferase is modified by reactive short and long chain aldehydes (13), and the ability of oxidatively modified HDL to promote cellular cholesterol efflux is diminished (14 -16), most probably due to alterations in its apolipoprotein moiety. During the acute phase response, up to 80% of apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, is displaced by serum amyloid A (17), and due to this exchange in the HDL apolipoprotein domain, native, anti-inflammatory HDL became proinflammatory during the acute phase response (18). The above mentioned results imply that HDL can protect LDL against oxidative modifications and could serve as a vehicle for detoxification of potentially (cyto)-toxic lipid hydroperoxides. However, under certain circumstances many of the important physiological properties of HDL can be lost during oxidation/modification, transforming HDL into a proatherogenic lipoprotein particle.

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