Low density lipoprotein (LDL) modification: basic concepts and relationship to atherosclerosis.
A large number of clinical studies support the hypothesis that the risk for atherosclerosis is associated with the proportion of different LDL subfractions in blood. Electronegatively modified forms of LDL (LDL(-)) isolated using different chromatographic techniques are characterised by significant differences in the protein and lipid content as compared to the native LDL subfraction. LDL(-) composition appears to influence its atherogenic properties as well as its high susceptibility to oxidation and impaired metabolism. Increased LDL(-) levels are found in subjects with coronary artery disease, particularly in diabetics and patients undergoing haemodialysis (HD). Whether elevated LDL(-) levels are due to the LDL oxidation in blood remains disputed despite the oxidative character of LDL(-) modification. Plausible means for LDL(-) formation in blood include glycation and protein-radical interactions with ApoB 100. The latter can prevail during HD as observed in in vitro studies using a model HD system. The rapid and progressive formation of LDL(-) during standard HD can be significantly reduced employing haemolipodialysis (HLD), which provides local delivery of specific antioxidants (vitamin E and C) to blood at concentrations above normal physiologic levels. This procedure appears to be more effective than oral supplementation with antioxidants and may be a promising approach to reducing the rapid progression of atherosclerosis in HD patients.
Sevanian
A
A
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, Calif 90033, USA. asevan@hsc.usc.edu
Asatryan
L
L
Ziouzenkova
O
O
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein