Differential effects of oxidized LDL on apolipoprotein AI and B synthesis in HepG2 cells.

Oxidized low-density lipoproteins (Ox-LDL) are key elements in atherogenesis. Apolipoprotein AI (apoAI) is an active component of the antiatherogenic high-density lipoproteins (HDL). In contrast, plasma apolipoprotein B (apoB), the main component of LDL, is highly correlated with coronary risk. Our results, obtained in HepG2 cells, show that Ox-LDL, unlike native LDL, leads to opposite effects on apoB and apoAI, namely a decrease in apoAI and an increase in apoB secretion as evaluated by [(3)H]leucine incorporation and specific immunoprecipitation. Parallel pulse-chase studies show that Ox-LDL impaired apoB degradation, whereas apoAI degradation was increased and mRNA levels were decreased. We also found that enhanced lipid biosynthesis of both triglycerides and cholesterol esters was involved in the Ox-LDL-induced increase in apoB secretion. Our data suggest that the increase in apoB and decrease in apoAI secretion may in part contribute to the known atherogenicity of Ox-LDL through an elevated LDL/HDL ratio, a strong predictor of coronary risk in patients.

Long-term moderate magnesium-deficient diet shows relationships between blood pressure, inflammation and oxidant stress defense in aging rats.

Epidemiological and experimental studies have indicated a relationship among aging, dietary Mg, inflammatory stress, and cardiovascular disease. Our aim in the present study was to investigate possible links between dietary Mg, oxidant stress parameters, and inflammatory status with aging in rats. We designed a long-term study in which rats were fed for 22 months with moderately deficient (150 mg/kg), standard (800 mg/kg), or supplemented (3200 mg/kg) Mg diets. Comparisons were made with young rats fed with the same diets for 1 month. Compared to the standard and supplemented diets, the Mg-deficient diet significantly increased blood pressure, plasma interleukin-6, fibrinogen, and erythrocyte lysophosphatidylcholine, particularly in aging rats, it decreased plasma albumin. The impairment of redox status was indicated by increases in plasma thiobarbituric acid reactive substances and oxysterols and an increased blood susceptibility to in vitro free-radical-induced hemolysis. We concluded that Mg deficiency induced a chronic impairment of redox status associated with inflammation which could significantly contribute to increased oxidized lipids and promote hypertension and vascular disorders with aging. Extrapolating to the human situation and given that Mg deficiency has been reported to be surprisingly common, particularly in the elderly, Mg supplementation might be useful as an adjuvant therapy in preventing cardiovascular disease.

Differential effects of cysteine and methionine residues in the antioxidant activity of human serum albumin.

Antioxidant properties of human serum albumin (HSA) may explain part of its beneficial role in various diseases related to free radical attack. In the present study, the antioxidant role of Cys and Met was studied by copper-mediated oxidation of human low density lipoproteins and by free radical-induced blood hemolysis which essentially assessed metal-chelating and free radical scavenging activities, respectively. Mild conditions were set up to specifically modify Cys and Met residues by N-ethylmaleimide (NEM) and chloramine T treatments, respectively. We found that Met and Cys accounted for 40-80% of total antioxidant activity of HSA. Copper binding to HSA was decreased by about 50% with chloramine T treatment of Met whereas no change was observed after NEM treatment of Cys. Although other amino acid residues are likely to be involved in anti-/prooxidant properties of HSA, from our data, we propose that Cys chiefly works as a free radical scavenger whereas Met mainly acts as a metal chelator.

(+)-Catechin inhibits platelet hyperactivity induced by an acute iron load in vivo.

Reactive oxygen species and platelets are thought to be involved in the pathogenesis of cardiovascular disease. Epidemiological data have indicated that high consumption of fruits and vegetables is associated with a lower incidence of vascular events. Polyphenols were proposed to provide such a protection. In the present study performed in rats, we investigated the influence of (+)-catechin (Cat), a polyphenol identified in tea, cocoa, and red wine, on an acute iron load-induced model of platelet hyperactivity. We found that platelet function was significantly enhanced in iron-loaded rats. These changes were associated with impairment of the antioxidative defense including ex vivo free radical-induced hemolysis. Pretreatment with Cat (10 mg/kg, ip, 4 d) normalized biomarkers of antioxidative status and platelet hyperactivity. The benefits of Cat treatment were only observed in iron-loaded animals and not in control animals. In light of the known antioxidant properties of Cat (or its metabolites), we suggest that oxidative injury-induced modification of platelet calcium homeostasis may have explained the iron load-induced platelet hyperactivity. The protective effect of Cat appears to work probably through normalization of the antioxidative status.