Low Density Lipoprotein (LDL) Modification: Basic Concepts and Relationship to Atherosclerosis

Abstract

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.

Identification of a Serum Component That Regulates Cyclooxygenase-2 Gene Expression in Cooperation with 4-Hydroxy-2-nonenal

“…G, enhanced production of prostaglandin E2 (PGE 2 ). RAW264.7 macrophages were treated with oxLDL (100 g/ml) and HNE (50 M) in the presence and absence of 10 M NS398 for 24 h. It has been shown that human plasma contains a denatured, electronegative LDL subfraction that possesses atherogenic properties and is associated with increased cardiovascular disease risk (23,24). Most mechanisms that describe the formation of such modified LDLs involve the oxidative modification of particles (19,20).…”

Why Hemodialysis Patients Are in a Prooxidant State? What Could Be Done to Correct the Pro/Antioxidant Imbalance

“…Hemolipodialysis is another quite innovative concept that consists in loading HD patients with vitamins E and C via the extracorporeal circuit during a HD session. Hydrophilic vitamin C is transferred by the dialysate while lipophilic vitamin E is delivered by an ancillary circuit consisting in vitamin E-rich liposomes [58,59]. The presence of liposomes facilitates vitamin E transfer from dialysate to blood but also enhances the removal of hydrophobic toxins such as leukotrienes, PAF acether and hydroperoxides which could participate in the oxidative stress [60] (fig.…”

LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein

“…Supplementary key words apolipoprotein B-100 • atherogenic low density lipoprotein • lipid peroxidation • oxidation • nitrotyrosine • unsaturated fatty acids • ␤ -strand structures • protein structure • secretory phospholipase A 2 Human plasma contains an electronegative LDL subfraction (LDL Ϫ ) that possesses atherogenic properties and is associated with increased cardiovascular disease risk (1,2). Increased levels of LDL Ϫ have been observed in hypercholesterolemic subjects (3), type 2 diabetics (4, 5), uremic subjects (6), after exhaustive physical exercise (7,8), and during postprandial lipemia (9).…”