Enhanced Levels of Lipoperoxides in Low Density Lipoprotein Incubated with Murine Fibroblasts Expressing High Levels of Human 15-Lipoxygenase

David J. Benz, Marc Mol, Masanori Ezaki, Natsuko Mori-Ito, Ildiko Zelán, Atsushi Miyanohara, Ted Friedmann, Sam Parthasarathy, Daniel Steinberg, Joseph L. Witztum
1995 Journal of Biological Chemistry  
There is strong experimental evidence that oxidized low density lipoprotein (Ox-LDL) plays an important role in atherosclerosis. However, the mechanisms by which Ox-LDL is formed in vivo are unknown. To test whether 15-lipoxygenase (15-LO) could play a role in oxidation of LDL by cells, we expressed 15-LO activity in murine fibroblasts, which do not normally have 15-LO activity, and tested their ability to modify LDL. Using a retroviral vector, we prepared fibroblasts that expressed 2-to
more » ... pressed 2-to 20-fold more 15-LO activity than control fibroblasts infected with a vector containing /3galactosidase (lacZ). Compared with LDL incubated with lacZ cells, LDL incubated with 15-LO-containing cells were enriched with lipid hydroperoxides. When these LDL samples were subsequently subjected to oxi dative stress, they were more susceptible to further ox idative modification, as judged by increased conjugated diene formation and by increased ability to compete with 125I-Ox-LDL for uptake by macrophages. These findings establish that cellular 15-LO can contribute to oxidative modification of LDL, but the quantitative sig nificance of these findings to the in vivo oxidation of LDL remains to be established.
doi:10.1074/jbc.270.10.5191 pmid:7890629 fatcat:ocanamykbneczho66dth3dx5mu