on December 12, 2002
Published online before print December 12, 2002, doi: 10.1161/01.ATV.0000051407.42536.73
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Submitted on October 21, 2002
Accepted on October 23, 2002
Phospholipid Hydroxyalkenals. Biological and Chemical Properties of Specific Oxidized Lipids Present in Atherosclerotic Lesions
Henry F. Hoff *;
From the Department of Cell Biology (H.F.H., J.O., Z.W., G.H.), Lerner Research Institute, Cleveland Clinic Foundation, and the Department of Chemistry (R.L.S.), Case Western Reserve University, Cleveland, Ohio.
* To whom correspondence should be addressed. E-mail: hoffh{at}ccf.org.
Objective—Phosphatidylcholine hydroxyalkenals (PC-HAs) are a class of oxidized PCs derived from lipid peroxidation of arachidonate or linoleate at the sn-2 position to form terminal 
-hydroxy, 
-, and 
-unsaturated aldehydes. The aim of this study was to characterize some of their biological properties, ascertain the mechanism of their action, and assess whether they have in vivo relevance.
Methods and Results—Combinations of cell biological approaches with radiolabels, mass spectroscopy, and immunochemical as well as immunohistochemical techniques were used to show that PC-HAs reduce the proteolytic degradation by mouse peritoneal macrophages (MPMs) of internalized macromolecules, such as maleylated bovine serum albumin, and that the activity of the lysosomal protease, cathepsin B, in MPMs form Michael adducts with MPM proteins and with N-acetylated cysteine in vitro form pyrrole adducts with MPM proteins and reduce the maturation of Rab5a, thereby impairing phagosome-lysosome fusion (maturation) in phagocytes; they are present unbound and as pyrrole adducts in human atherosclerotic lesions.
Conclusions—PC-HAs are present in vivo and possess multiple functions characteristic of oxidized LDL and 4-hydroxynonenal.
Key words: oxidized phospholipids • macrophages • intracellular degradation • biochemical adducts • atherosclerotic lesions • Rab5
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