Basic research in antioxidant inhibition of steps in atherogenesis.
Oxidised low-density lipoprotein (LDL) contributes to atherogenesis by a number of mechanisms, and antioxidants may act as anti-atherogens. LDL oxidation is inhibited by LDL-associated antioxidants, particularly alpha-tocopherol (vitamin E), and water-soluble antioxidants present in LDL's biologic milieu, especially ascorbate (vitamin C). In addition to protecting LDL against oxidation, antioxidants may act at the level of the vascular cell by limiting cellular production of reactive oxygen species, and, thus, cell-mediated LDL oxidation. Cellular antioxidants can also protect against vascular cell dysfunction that would otherwise promote atherogenesis, such as increased adhesion molecule expression and monocyte recruitment, impaired production or release of nitric oxide, or both, and the proliferation of smooth muscle cells. Some of these processes are regulated by nuclear factor-kappa B or related transcription factors, which are redox-sensitive and inhibited by antioxidants. Furthermore, cellular antioxidants can limit cytotoxic effects of oxidised LDL and other oxidant insults, inhibiting vascular cell necrosis and lesion progression. Finally, some antioxidants, in particular alpha-tocopherol, may affect atherogenesis by inhibiting platelet function and mural thrombosis, although this effect appears to be explained by the inhibition of protein kinase C independent of alpha-tocopherol's antioxidant activity.
Gokce
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N
Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts 02118, USA.
Frei
B
B
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D003327:Coronary Disease / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D013927:Thrombosis / Q000517:prevention & control; D019010:Vascular Cell Adhesion Molecule-1
D000975:Antioxidants; D008077:Lipoproteins, LDL; D019010:Vascular Cell Adhesion Molecule-1