Oxidized monocyte-derived macrophages in aortic atherosclerotic lesion from apolipoprotein E-deficient mice and from human carotid artery contain lipid peroxides and oxysterols

Oxidative stress is thought to play an important role in atherogenesis. The present study demonstrated, for the first time, that macrophages (original ly derived from blood monocytes) isolated from aortas of the atheroscleroti c apolipoprotein E deficient (E degrees) mice or from human carotid artery, are oxidized as they contain lipid peroxides and oxysterols. The major oxy sterol in arterial macrophages was found to be 7-ketocholesterol (51% of to tal oxysterols). To find out whether lipid peroxidation of monocytes occurs in vivo already in the blood, we analyzed the oxidative state of monocytes derived from E degrees mice in comparison to monocytes from control mice. Cellular lipid peroxides and total oxysterols were four and sevenfold highe r respectively, in monocytes derived from E degrees mice in comparison to m onocytes from control mice. The results of the present study thus demonstra ted the presence of lipid-peroxidized monocytes already in the blood, which are further oxidized in the arterial wall after their conversion into macr ophages. The arterial oxidized macrophages could be considered key contribu tors to foam cell formation, the hallmark of early atherosclerosis, 2000 Ac ademic Press.