New Insight on the Relationship between LDL Composition, Associated Proteins, Oxidative Resistance and Preparation Procedure

• Published in: Free radical research 2002-02, Vol.36 (2), p.127-142
• Main Authors: Carbonneau, Marie-Annette, Cartron, Emeline, Leger, Claude-Louis, Senglat, Christiane, Descomps, Bernard
• Format: Article
• Language: English
• Subjects: Adult; Albumin-associated Ldl; Cholesterol, LDL - chemistry; Cholesterol, LDL - metabolism; Chromatography, Gel; Copper - metabolism; Copper - pharmacology; Electrophoresis, Polyacrylamide Gel; Humans; Kinetics; Ldl Chemical Composition; Ldl Cu 2+ -oxidation Resistance; Ldl-phospholipase A 2; Male; Oxidation-Reduction - drug effects; Phospholipases A - metabolism; Platelet Activating Factor-acetylhydrolase; Serum Albumin - metabolism; Time Factors; Ultracentrifugation; Vitamin E; Vitamin E - pharmacology
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715760290006466

Oxidized low density lipoprotein (LDL) plays an important role in atherogenesis. It is generally thought that LDL is mainly oxidized in the intima of vessel walls, surrounded by hydrophilic antioxidants and proteins such as albumin. The aim of this study was to investigate the possible interrelationships between oxidation resistance of LDL and its protein and lipid moieties. Proteins and to a lesser extent lipids, appeared to be the major determinants in the LDL Cu 2+ -oxidation resistance, which in turn depend on the ultracentrifugation (UC) procedure used. Comparing high speed/short time (HS/ST, 4 &#117 h), high speed/long time (HS/LT, 6-16 &#117 h) and low speed/long time (LS/LT, 24 &#117 h) conditions of UC, HS with the shortest time (4 &#117 h) led to prepare LDL (named LDL·HS-4 &#117 h) with higher total protein and triglyceride contents, unchanged total cholesterol, phospholipids and Vitamin E, and higher Cu 2+ -oxidation resistance. Among proteins, only albumin allows to explain changes. PAF acetyl hydrolase appeared to be unaffected, whereas its pro-oxidant role was established and found only in the absence of albumin. In contrast the pro-oxidant role of caeruloplasmin took place regardless of the albumin content of LDL. The antioxidant effect of albumin (the oxidation lag time was doubled for 20 &#117 mol/mol albumin per LDL) is assumed to be due to its capacity at decreasing LDL affinity for Cu 2+ . Interestingly, the LDL·HS-4 &#117 h albumin content mirrored the intrinsic characteristics of LDL in the plasma and was not affected by added free albumin. Moreover, it has been verified that in 121 healthy subjects albumin was the best resistance predictor of the Cu 2+ -oxidation of LDL·HS-4 &#117 h, with a multiple regression equation: lag time (min)=62.1+0.67(HSA/apoB)+0.02 (TG/apoB) &#109 0.01(TC/apoB); r =0.54, P