The article by Witztum and Steinberg discusses the role of oxidative modification of low-density lipoprotein (LDL) in atherogenesis. They highlight that while lowering plasma cholesterol is effective in slowing the progression of coronary atherosclerosis, the cellular and molecular mechanisms linking hypercholesterolemia to atherogenesis remain unclear. The authors emphasize that oxidative modification of LDL is a critical step in the atherogenic process, as it enhances the uptake of LDL by macrophages, leading to cholesterol accumulation and foam cell formation. They review the evidence for the presence of oxidized LDL (Ox-LDL) in atherosclerotic tissues and the protective effects of antioxidants like probucol and butylated hydroxytoluene. The article also explores the potential mechanisms by which Ox-LDL contributes to atherogenesis, including its ability to recruit monocytes, alter gene expression, and affect vasomotor properties. Additionally, the authors discuss factors that influence LDL oxidation in vivo, such as dietary composition, antioxidant content, and the activity of enzymes like phospholipase A2. Finally, they propose measures to inhibit oxidative modification, including dietary interventions and the use of antioxidants, and suggest that these approaches could complement cholesterol-lowering therapies to prevent atherosclerosis and its complications.The article by Witztum and Steinberg discusses the role of oxidative modification of low-density lipoprotein (LDL) in atherogenesis. They highlight that while lowering plasma cholesterol is effective in slowing the progression of coronary atherosclerosis, the cellular and molecular mechanisms linking hypercholesterolemia to atherogenesis remain unclear. The authors emphasize that oxidative modification of LDL is a critical step in the atherogenic process, as it enhances the uptake of LDL by macrophages, leading to cholesterol accumulation and foam cell formation. They review the evidence for the presence of oxidized LDL (Ox-LDL) in atherosclerotic tissues and the protective effects of antioxidants like probucol and butylated hydroxytoluene. The article also explores the potential mechanisms by which Ox-LDL contributes to atherogenesis, including its ability to recruit monocytes, alter gene expression, and affect vasomotor properties. Additionally, the authors discuss factors that influence LDL oxidation in vivo, such as dietary composition, antioxidant content, and the activity of enzymes like phospholipase A2. Finally, they propose measures to inhibit oxidative modification, including dietary interventions and the use of antioxidants, and suggest that these approaches could complement cholesterol-lowering therapies to prevent atherosclerosis and its complications.