Oxidative stress and atherosclerosis

Cardiovascular disease is the leading cause of death in westernized populat ions. Accumulating evidence suggests that lipid peroxidation is pivotal in atherogenesis. Supplementation with antioxidants, e.g., vitamin E, has been shown in animal models and humans to reduce atherosclerotic lesion progres sion and cardiovascular events. Methods to evaluate oxidative stress includ e direct and indirect measures. The most relevant direct measure of oxidati ve stress is urinary F-2-isoprostanes, which are prostaglandin-like compoun ds formed in vivo from free radical catalyzed peroxidation of arachidonic a cid via a non-cycloxygenase-dependent mechanism. The measurement of F-2-iso prostanes provides a sensitive, specific, and non-invasive method for the a ssessment of in vivo lipid peroxidation. Other direct measures include auto antibodies to oxidized LDL, and assaying modified LDL in plasma, breath vol atile hydrocarbons, and protein carbonyl. Measures of autoantibodies and mo dified LDL still need further standardization before they can be specific a nd sensitive direct measures of oxidative stress. Indirect measures of oxid ative stress include measurement of total antioxidant capacity (ORAC, TRAP) , individual antioxidant status (including glutathione, alpha-tocopherol, c arotenoids, and ascorbate) and LDL oxidizability (including conjugated dien es, lipid peroxides, TBARS, apo B-100 fluorescence, and fatty acid content) .