Oxidative modification of
low-density lipoprotein (
LDL) is one of the critical steps for the development of
atherosclerosis. Accumulating studies have indicated that 12/
15-lipoxygenase highly expressed in macrophages plays an essential role in the oxidation of circulating
LDL. It has been demonstrated that
LDL needs to bind the
LDL receptor-related protein (LRP), a
cell-surface receptor, prior to its oxidation by 12/
15-lipoxygenase expressed in macrophages. LRP is suggested to mediate the selective transfer of
cholesteryl ester in
LDL to the plasma membrane of macrophages without endocytosis and degradation of the
LDL particle. At the same time, binding of
LDL to LRP translocates the 12/
15-lipoxygenase from the cytosol to the plasma membrane. It is also demonstrated that
5-lipoxygenase localized in macrophages generates
leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues and contribute to lesion development. Therefore, the inhibition of these
lipoxygenases may be effective in the prevention and treatment of the inflammatory diseases.