Low-density lipoprotein (LDL) oxidation plays a significant role in atherogenesis. Initially considered a minor issue in lipoprotein metabolism, oxidative modification of LDL has been shown to contribute to the formation of foam cells and the progression of atherosclerosis. Oxidized LDL (OxLDL) is recognized by scavenger receptors and can induce cholesterol accumulation in macrophages. It is also a chemotactic agent for monocytes and can inhibit macrophage motility. OxLDL is cytotoxic to endothelial cells, inhibits vasodilation, and can stimulate the release of MCP-1 and MCSF, which promote macrophage differentiation. Additionally, OxLDL is immunogenic and can lead to the formation of autoantibodies. These properties suggest that oxidative modification of LDL contributes to atherosclerosis through multiple mechanisms. OxLDL can be generated through cell-mediated oxidative modification, which is influenced by factors such as transition metals and antioxidants. The degree of oxidation varies, with minimally oxidized LDL (MM-LDL) having different biological effects compared to maximally oxidized LDL. OxLDL is found in atherosclerotic lesions and is recognized by scavenger receptors, including the acetyl LDL receptor (now known as scavenger receptor A, SRA). Other scavenger receptors, such as CD36, also bind OxLDL and may contribute to foam cell formation. In vivo, LDL oxidation occurs in sequestered microenvironments where antioxidants are less effective. OxLDL is rapidly cleared from the bloodstream by hepatic cells, while MM-LDL may accumulate. Enzymes such as NADPH oxidase, 15-lipoxygenase, and myeloperoxidase are involved in LDL oxidation, with lipoxygenases and myeloperoxidase playing significant roles in atherosclerotic lesions. Antioxidants such as vitamin E and probucol have been shown to inhibit atherogenesis in experimental models. However, clinical trials have shown mixed results, with some antioxidants showing protective effects against cardiovascular events. The effectiveness of antioxidants in humans is still under investigation, and the threshold for antioxidant activity required to prevent atherosclerosis remains unclear. Receptors for OxLDL, including SRA and CD36, are involved in the uptake of OxLDL by macrophages and may also recognize apoptotic cells. The persistence of these receptors in evolution suggests they may have roles beyond atherosclerosis, such as in recognizing damaged cells. OxLDL's role in human disease is supported by its presence in atherosclerotic lesions and the negative correlation between antioxidant intake and cardiovascular risk. However, the time scale of lesion development in humans is much longer than in animal models, complicating the translation of findings to clinical practice.Low-density lipoprotein (LDL) oxidation plays a significant role in atherogenesis. Initially considered a minor issue in lipoprotein metabolism, oxidative modification of LDL has been shown to contribute to the formation of foam cells and the progression of atherosclerosis. Oxidized LDL (OxLDL) is recognized by scavenger receptors and can induce cholesterol accumulation in macrophages. It is also a chemotactic agent for monocytes and can inhibit macrophage motility. OxLDL is cytotoxic to endothelial cells, inhibits vasodilation, and can stimulate the release of MCP-1 and MCSF, which promote macrophage differentiation. Additionally, OxLDL is immunogenic and can lead to the formation of autoantibodies. These properties suggest that oxidative modification of LDL contributes to atherosclerosis through multiple mechanisms. OxLDL can be generated through cell-mediated oxidative modification, which is influenced by factors such as transition metals and antioxidants. The degree of oxidation varies, with minimally oxidized LDL (MM-LDL) having different biological effects compared to maximally oxidized LDL. OxLDL is found in atherosclerotic lesions and is recognized by scavenger receptors, including the acetyl LDL receptor (now known as scavenger receptor A, SRA). Other scavenger receptors, such as CD36, also bind OxLDL and may contribute to foam cell formation. In vivo, LDL oxidation occurs in sequestered microenvironments where antioxidants are less effective. OxLDL is rapidly cleared from the bloodstream by hepatic cells, while MM-LDL may accumulate. Enzymes such as NADPH oxidase, 15-lipoxygenase, and myeloperoxidase are involved in LDL oxidation, with lipoxygenases and myeloperoxidase playing significant roles in atherosclerotic lesions. Antioxidants such as vitamin E and probucol have been shown to inhibit atherogenesis in experimental models. However, clinical trials have shown mixed results, with some antioxidants showing protective effects against cardiovascular events. The effectiveness of antioxidants in humans is still under investigation, and the threshold for antioxidant activity required to prevent atherosclerosis remains unclear. Receptors for OxLDL, including SRA and CD36, are involved in the uptake of OxLDL by macrophages and may also recognize apoptotic cells. The persistence of these receptors in evolution suggests they may have roles beyond atherosclerosis, such as in recognizing damaged cells. OxLDL's role in human disease is supported by its presence in atherosclerotic lesions and the negative correlation between antioxidant intake and cardiovascular risk. However, the time scale of lesion development in humans is much longer than in animal models, complicating the translation of findings to clinical practice.