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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:275.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Phospholipid Hydroxyalkenals

Biological and Chemical Properties of Specific Oxidized Lipids Present in Atherosclerotic Lesions

Henry F. Hoff; June O’Neil; Zhiping Wu; George Hoppe; Robert L. Salomon

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.

Correspondence to Henry F. Hoff, PhD, Department of Cell Biology, Lerner Research Institute, NC-10, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. 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 ß-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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