The article by Daniel Steinberg discusses the significance of low-density lipoprotein (LDL) oxidation in atherogenesis. Initially, it was known that LDL is highly susceptible to oxidative damage, but this was not initially considered a major issue. However, recent evidence suggests that the oxidation of LDL plays a crucial role in the development of atherosclerosis. Key points include: 1. **Oxidation of LDL**: LDL can be modified by cells, such as endothelial cells and smooth muscle cells, to form forms that are more rapidly taken up by macrophages and capable of increasing cellular cholesterol content. This modification is primarily due to oxidative processes. 2. **Pathobiological Significance**: Oxidized LDL (OxLDL) is recognized by scavenger receptors, leading to foam cell formation and the initiation or acceleration of atherosclerotic lesions. 3. **Additional Properties of OxLDL**: OxLDL has multiple proatherogenic properties, including chemotaxis for monocytes, inhibition of macrophage motility, cytotoxicity for endothelial cells, and immunogenicity. 4. **Nature of OxLDL**: OxLDL is defined by its biological properties, such as its recognition by scavenger receptors and its rapid uptake by macrophages. It can be minimally oxidized (NM-LDL) or maximally oxidized (maximally oxidized LDL), with varying degrees of oxidation. 5. **In Vivo Oxidation**: OxLDL is oxidized in sequestered microenvironments within arterial lesions, where antioxidants are less effective. Antioxidants can slow the progression of atherosclerosis in experimental models. 6. **Receptors for OxLDL**: OxLDL is bound and internalized by scavenger receptors, including the acetyl LDL receptor (SRA) and CD36. These receptors play a significant role in atherogenesis. 7. **Clinical Relevance**: Antioxidants, such as vitamin E, have been shown to protect circulating LDL from oxidation and slow the progression of atherosclerosis in humans. However, clinical trials using β-carotene have been less effective. The article emphasizes the importance of understanding the oxidative modification of LDL and its role in atherogenesis, highlighting the potential for antioxidant interventions to slow the progression of the disease.The article by Daniel Steinberg discusses the significance of low-density lipoprotein (LDL) oxidation in atherogenesis. Initially, it was known that LDL is highly susceptible to oxidative damage, but this was not initially considered a major issue. However, recent evidence suggests that the oxidation of LDL plays a crucial role in the development of atherosclerosis. Key points include: 1. **Oxidation of LDL**: LDL can be modified by cells, such as endothelial cells and smooth muscle cells, to form forms that are more rapidly taken up by macrophages and capable of increasing cellular cholesterol content. This modification is primarily due to oxidative processes. 2. **Pathobiological Significance**: Oxidized LDL (OxLDL) is recognized by scavenger receptors, leading to foam cell formation and the initiation or acceleration of atherosclerotic lesions. 3. **Additional Properties of OxLDL**: OxLDL has multiple proatherogenic properties, including chemotaxis for monocytes, inhibition of macrophage motility, cytotoxicity for endothelial cells, and immunogenicity. 4. **Nature of OxLDL**: OxLDL is defined by its biological properties, such as its recognition by scavenger receptors and its rapid uptake by macrophages. It can be minimally oxidized (NM-LDL) or maximally oxidized (maximally oxidized LDL), with varying degrees of oxidation. 5. **In Vivo Oxidation**: OxLDL is oxidized in sequestered microenvironments within arterial lesions, where antioxidants are less effective. Antioxidants can slow the progression of atherosclerosis in experimental models. 6. **Receptors for OxLDL**: OxLDL is bound and internalized by scavenger receptors, including the acetyl LDL receptor (SRA) and CD36. These receptors play a significant role in atherogenesis. 7. **Clinical Relevance**: Antioxidants, such as vitamin E, have been shown to protect circulating LDL from oxidation and slow the progression of atherosclerosis in humans. However, clinical trials using β-carotene have been less effective. The article emphasizes the importance of understanding the oxidative modification of LDL and its role in atherogenesis, highlighting the potential for antioxidant interventions to slow the progression of the disease.