Oxidation of low-density lipoprotein in atherosclerosis from basic biochemistry to clinical studies.
Although it has been known for long time that atherosclerosis is associated with lipid deposition, only recently it has been accepted that the plasmatic concentration of cholesterol, especially LDL cholesterol, is a risk factor for atherosclerosis. However, chemically modified LDL, but not native LDL, is able to induce the formation of foam cells, the hallmark of atherosclerosis. LDL oxidation is likely to be the most important form of LDL modification in humans. In biochemical terms, LDL oxidation is a free radical driven chain reaction where polyunsaturated fatty acids are converted to lipid peroxides, which easily decompose to many products, including biologically active aldehydes. The assay of LDL oxidation in biological fluids is problematic; direct assays detect a product of LDL oxidation whereas indirect assays give an indicator of LDL oxidation susceptibility. In general, epidemiological studies support the concept that the level of plasmatic lipophilic antioxidants, tocopherols and carotenoids, is low in populations at increased risk for atherosclerosis. However, clinical trials based on vitamin E as antioxidant showed inconclusive results, suggesting that supplementation with vitamin E is not generically recommended for atherosclerotic patients. These results, however, do not contradict that oxidation of lipoprotein is involved in atherosclerosis; rather, this negative outcome raises a number of considerations such as the need for a reliable marker of lipoprotein oxidation in plasma and a more complete information about the physiological triggers of lipoprotein oxidation.
Albertini
R
R
Laboratory of Clinical Chemistry, IRCCS Policlinico San Matteo, Pavia, Italy. riccardo_albertini@hotmail.com
Moratti
R
R
De Luca
G
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism*; D013997:Time Factors; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D008078:Cholesterol, LDL; D005609:Free Radicals; D008077:Lipoproteins, LDL; D014810:Vitamin E; D010100:Oxygen