Possible in vivo behavior of OxLDL. (a) The temporal rise and fall of plasma OxLDL levels suggest that MM-LDL (OxLDL) may be transferred between the vessel wall tissues and circulation in the early stages of atherogenesis. In this stage, circulating OxLDL is likely to be MM-LDL, since heavily oxidized LDL is very rapidly cleared from the circulation. The tissues of the vessel wall could be the site of LDL oxidation, but further study is needed to examine whether oxidation proceeds in apparently healthy vessel walls during the very early stages. When the plasma OxLDL level decreases atherosclerotic lesions appear to develop. (b) In advanced stages, many macrophages and foam cells are found in the atherosclerotic lesions. MM-LDL could be further modified to form OxLDL in the lesions. OxLDL is taken up by macrophages, and processed in the lysosomes. Some of the OxLDL is completely degraded, and a part of OxLDL is relatively resistant to proteolytic processing. Partially degraded OxLDL particles are observed in the lesions. (c) Upon plaque rupture, or when an atherosclerotic plaque is injured by PTCA treatment, OxLDL and partially degraded OxLDL are rapidly released from the lesions into the circulation, which causes a temporal rise of the plasma OxLDL level.
