Smoking cessation increases the resistance of low-density lipoprotein to oxidation

The effects of smoking cessation on the susceptibility to oxidation of low-density lipoprotein (LDL) was investigated in 14 men who quit smoking for 3 months. LDL was isolated and susceptibility of LDL to V-70 (4-methoxy-2,4-dimethylvalerinitrile)-mediated oxidation was assessed by measuring conjugated diene production at 234 nm, the lag phase being a measure of the resistance of LDL to oxidation. The mean duration of the lag phase became 1.9-fold longer after 3 months (P<0.001). The result suggests that the increase in resistance of LDL to oxidation contributes to the reduction of the risk of coronary heart disease by smoking cessation.     

Baseline level and change in serum albumin concentration and the risk of incident type 2 diabetes

Aims

We aimed to determine whether baseline level and change in serum albumin concentration are predictive of future development of type 2 diabetes (T2D).

Impact of glycation on structural and antioxidant function of human serum albumin: Relevance in diabetic complications

AimNon-enzymatic glycation impairs the structural and functional characterstics of human serum albumin (HSA) native conformation. Prolonged hyperglycemia causes cross links formation in proteins that may contribute to progression of diabetic complications.MethodsHSA (20 μM) was incubated with different concentration of d-glucose100, 200, 300 and 400 mg/dl for a period of 40 days in phosphate buffer saline (20 mM pH = 7.4) under sterile conditions. Incubated samples were extensively dialyzed and structural changes were analyzed by far and near UV circular dichroism spectra measurement. Fructosamine assay with nitroblue tetrazolonium was performed to confer isomerisation between glucose and protein. Aggregations of the glycated product (AGEs) formed during reduction of nitrobluetetrazolium dye were evaluated by transmission electron microscopy. Crosslinks aggregates were investigated by in-situ Congo red binding assay. Red blood cells hemolysis test was performed to decipher the antioxidant activity of albumin samples.ResultsFructosamine content in glycated albumin demonstrates the non-enzymatic addition of glucose to HSA and confers the formation of monoformazone (marker of glycation). Significant changes were found in the glycated samples of HSA compared to native (unmodified) in far and near UV circular dichroism. Transmission electron microscopy, Congo red staining, showed the formation of crosslink's aggregated mass in glycated HSA. Glycation of albumin reduces the antioxidant capacity of native albumin confirmed by red blood cells hemolysis test.ConclusionThe finding of present study brings new evidences on the detrimental alterations of on albumin vital functions after non-enzymatic glycation with glucose. These results may emphasize the albumin associated diabetic complications under glycemic range of diabetes mellitus.     

Cytoprotective antioxidant activity of serum albumin and autocrine catalase in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) cells are long lived in vivo but undergo spontaneous apoptosis when cultured in vitro. Intriguingly, CLL cells also appear to have a specific susceptibility to oxidative stress - a potent inducer of apoptosis. Here, we show that serum albumin can function as a cytoprotective antioxidant of potential relevance to circulating CLL cells, and that autocrine catalase - a hydrogen peroxide-inactivating enzyme that may be released extracellularly - can perform a similar role under the crowded conditions that prevail at sites of tissue involvement. Albumin lowered oxidative stress in cultured CLL cells and inhibited spontaneous and reactive oxidant-induced apoptosis. Maximal effects were observed at a concentration of 10 mg/ml - fourfold lower than that in plasma and twofold higher than that in standard culture medium containing 10% fetal calf serum. Oxidative stress and spontaneous apoptosis were also decreased by cell crowding and by conditioned medium (CM) from crowded CLL cells, indicating that these processes were subject to autocrine regulation. CLL cells were found to express catalase and release enzyme activity into the culture medium. Exogenous catalase decreased oxidative stress and spontaneous apoptosis, and the anti-apoptotic effect of CM from crowded CLL cells was abrogated by the specific catalase inhibitor, 3'-amino-1,2,4-triazole. Together, these data strongly implicate autocrine catalase as a cytoprotective antioxidant. Oxidative stress in CLL cells was greatly diminished by ruthenium red - an inhibitor of mitochondrial reactive oxidant production - and by the glutathione (GSH) precursor N-acetylcysteine, suggesting that the GSH peroxidase antioxidant system may be compromised by lack of available substrate. Our findings highlight the importance of endogenous reactive oxidants in regulating CLL-cell apoptosis, and help to explain why CLL cells survive for prolonged periods in vivo despite their vulnerability to oxidative stress and spontaneous apoptosis when cultured in vitro.     

Susceptibility of apolipoprotein B-containing lipoproteins to oxidation and antioxidant status in acute coronary syndromes

BACKGROUND: Oxidized lipoproteins may play an important role in the pathogenesis of atherosclerosis, and it has been shown that antioxidants have a protective effect against the progression of atherosclerosis. HYPOTHESIS: The aim of this study was to investigate the oxidative susceptibility of apolipoprotein B-containing lipoproteins and antioxidant status in patients with acute coronary syndromes and chronic stable angina pectoris. METHODS: The study population included 70 patients with acute coronary syndromes (14 with recent acute myocardial infarction and 56 with unstable angina pectoris), 105 patients with stable angina pectoris, and 75 control subjects. In addition to conventional lipid and lipoprotein analysis, the susceptibility of apolipoprotein B-containing lipoproteins to in vitro oxidation (lag phase) and plasma vitamin E and total carotene levels was measured. RESULTS: The lag phase was significantly shorter in patients with acute coronary syndromes (45 +/- 12 min) than in patients with stable angina pectoris (51 +/- 10 min) and in control subjects (58 +/- 9 min) (p < 0.0001). Both plasma vitamin E and total carotene levels were lowest in patients with acute coronary syndromes (1.11 +/- 0.32 mg/dl and 119 +/- 32 micrograms/dl, respectively), followed by patients with stable angina pectoris (1.25 +/- 0.37 mg/dl and 132 +/- 37 micrograms/dl) and then controls (1.52 +/- 0.31 mg/dl and 167 +/- 41 micrograms/dl). CONCLUSIONS: These data suggest that there is an intense oxidative process and a lower antioxidant status in acute coronary syndromes. This may lead to plaque instability due to the activation of the inflammatory response in coronary atherosclerotic lesions.     

Ascorbate and urate are the strongest determinants of plasma antioxidative capacity and serum lipid resistance to oxidation in Finnish men

Copper-induced plasma lipoprotein oxidation resistance has usually been determined in separated low density lipoprotein (LDL) fractions, that do not contain water-soluble antioxidants present in blood plasma. The aim of this study was to find the main determinants of the measurements of copper-induced lipid oxidation resistance (lag time) in whole serum and plasma total peroxyl radical trapping capacity (TRAP) in a population sample of smoking (n=25) or non-smoking (n=26) middle aged men at high risk of cardiovascular diseases. Smokers had significantly lower plasma ascorbic acid values, but only slightly lower -tocopherol, β-carotene and serum urate values than non-smokers. Plasma ascorbic acid concentration explained 23.5% of the lag time variation (standardized regression coefficient β=0.48; P=0.004) in smokers and 5.6% in non-smokers. Serum urate concentration was the strongest determinant of lag time in non-smokers (β=0.64, P<0.001). In addition, serum albumin, lipid standardized -tocopherol and serum high density lipoprotein (HDL) cholesterol entered the multivariate regression model for lag time. For plasma TRAP, only urate and ascorbic acid entered the multivariate regression model. Lag times in serum and in isolated very low density lipoprotein (VLDL) and LDL fraction did not correlate, but the maximal rate of these reactions correlated significantly. These results confirm that lipid peroxidation resistance in serum or plasma are associated with ascorbic acid, urate, -tocopherol, albumin and HDL concentrations. The measurement of lipid oxidation resistance in whole serum might be more physiological than in isolated lipoprotein fraction, as the effects of water-soluble antioxidants are not artificially removed.     

Response of adipose tissue lipoprotein lipase activity and serum lipoproteins to acute hyperinsulinaemia in man

Summary In order to assess the short-term effects of hyperinsulinaemia and hyperglycaemia on adipose tissue lipoprotein lipase activity and on serum lipoproteins, we measured these variables in ten normal subjects during euglycaemic and hyperglycaemic hyperinsulinaemic clamps. The mean steady-state plasma glucose and insulin concentrations, respectively, were 4.7 mmol/l and 101 mU/l during euglycaemic moderate-insulin clamp, 4.9 mmol/l and 565 mU/l during euglycaemic high-insulin clamp, and 8.8 mmol/l and 148 mU/l during hyperglycaemic clamp. Saline infusion was used as control. The adipose tissue lipoprotein lipase activity rose significantly over 5 h during high-insulin clamp (p<0.01) and during hyperglycaemic clamp (p<0.05), but did not change during the moderate-insulin clamp. The magnitude of change of lipoprotein lipase activity from baseline (either rise or fall) was inversely related to the preclamp activity during euglycaemic moderate-insulin clamp (r= -0.67), during hyperglycaemic clamp (r= -0.68) and during infusion of saline (r= -0.75, p<0.05). Total serum triglyceride concentration decreased significantly during all clamp studies compared with the control experiment. This change was mainly accounted for by a decrease of VLDL triglyceride. The LDL cholesterol level fell by an average of 5% (p<0.05) during the high-insulin clamp and by 10% (p<0.05) during the hyperglycaemic clamp. The HDL cholesterol level did not change significantly. It is concluded that adipose tissue lipoprotein lipase activity in man is increased by physiological insulin levels during hyperglycaemia and also by supraphysiological insulin levels during euglycaemia, but is not influenced by physiological hyperinsulinaemia without hyperglycaemia. Low basal lipoprotein lipase activity is more sensitive to insulin-glucose stimulation than primarily high lipoprotein lipase activity. Acute hyperinsulinaemia decreases VLDL triglyceride and LDL cholesterol concentrations.