Susceptibility of LDL to oxidation in vitro and antioxidant capacity in familial combined hyperlipidemia: comparison of patients with different lipid phenotypes

BACKGROUND: There is increasing evidence that oxidation of low-density lipoprotein (LDL) plays an important role in atherogenesis. AIM: To explore the LDL oxidizability and its determinants in familial combined hyperlipidemia (FCHL) patients with different phenotypes. METHOD: The study included 59 FCHL family members with different lipid phenotypes, 39 non-affected relatives, and 30 spouses as healthy controls. RESULTS: The lag time for LDL oxidation was significantly shorter in FCHL patients with different lipid phenotypes as compared to healthy controls. There were no significant differences in the propagation rate and conjugated diene formation and alpha-tocopherol content in LDL between the FCHL groups and healthy controls. Plasma concentrations of alpha-tocopherol in all FCHL patients and uric acid in FCHL patients with IIB and IV phenotypes were significantly higher than in healthy controls. Plasma total peroxyl radical trapping capacity measured (TRAPmea) and TRAPcalc tended to be higher in affected FCHL groups, but the difference was significant only for IIB phenotype. The peak LDL particle size in the combined group of FCHL patients was significantly smaller than in healthy controls. The lag time for LDL oxidation correlated significantly with LDL size both in the group of FCHL family members (r = 0.477, P<0.001) and in the healthy controls (r = 0.482, P<0.01). CONCLUSIONS: LDL from FCHL patients irrespectively of lipid phenotypes is more susceptible to oxidation in vitro than LDL from healthy controls. This increased susceptibility of LDL to oxidation in vitro seems to be attributed to the abundance of small dense LDL particles and not to the defect of antioxidant capacity in FCHL     

Effects of preventive group education on the resistance of LDL against oxidation and risk factors for coronary heart disease in bypass surgery patients

BACKGROUND. Comprehensive preventive education for heart patients is effective in reducing cardiac events. However, very demanding counselling protocols cannot easily be implemented as an integral part of clinical practice in hospitals. AIM. To evaluate whether recurrent preventive group education for coronary artery bypass grafting patients affects the resistance of LDL against oxidation and the classical risk factors for coronary heart disease. METHODS. A prospective, controlled study with one-year follow-up was carried out in Southern Finland. Coronary artery bypass patients were allocated late ( &#83 18 months) after the operation in the intervention and control groups. RESULTS. Seventy two patients (65 men and 7 women) completed the study. Twelve-hour group education on healthy life-style had a significant (25%, P = 0.01) but transient positive effect on the resistance of LDL against oxidation. There was a trend towards increased physical activity in the intervention group. The impact of education on patients' weight was also more consistent (1.2 kg at 12 months, P < 0.05), whereas long-term effects on fibrinogen and serum lipids were small. CONCLUSIONS. Repeated group education applied as an economically feasible part of specialist care had only small positive effects on patients' risk factors. There was a significant, but transient, increase in the resistance of LDL against oxidation. However, effective lipid lowering drug treatment is indicated for most coronary artery bypass patients rather than repeated health education alone.     

Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinaemia

Abstract. The pathobiochemical mechanism of arteriosclerosis in hyperhomocysteinaemia has not yet been elucidated. In vitro studies have shown that the cytotoxic properties of homocysteine can be ascribed to its generation of reactive oxygen species. We studied lipid peroxidation, both in vivo and in vitro , in 10 homozygous cystathionine synthase-deficient (CSD) patients and in a control group of 10 healthy subjects of comparable age and sex. The susceptibility of low-density lipoprotein (LDL) from hyperhomo-cysteinaemic patients to oxidation was determined in vitro by continuously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed as total diene production) of LDL from CSD patients were not significantly different from those of LDL from controls. Furthermore, the time needed to reach maximal diene production, i.e. t(max), was similar for LDL from patients and controls. In addition, the vitamin E concentrations in LDL of CSD patients and controls were similar. The mean concentration (± SD) of plasma thiobarbituric acid reactive substances (TBARS), an indicator of in vivo lipid peroxidation, was 2.2 ± 0.7 μmol L^-1 in CSD patients, a lower value than that measured in the matched controls (50± 2.0 μmol L^-1). Investigation of in vivo and in vitro parameters of lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomocysteinaemia is unlikely to be due to increased lipid peroxidation.     

Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia

Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P相似文献   

Increased uptake of oxidized LDL by macrophages from type 2 diabetics is inhibited by polyamines

The aim of this study was to evaluate the effect of polyamines putrescine, spermidine and spermine on human LDL oxidation and to assess the ability of macrophages derived from type 2 diabetic patients to uptake oxLDL. Polyamine effect was compared with α-tocopherol. Four healthy subjects and eight type 2 diabetic patients were included in this study. To characterize type 2 diabetic patients and non-diabetic subjects, laboratory test were carried out. Glucose, glycated haemoglobin (HbA_1C), triglycerides, low (LDL) and high density lipoproteins (HDL) and serum lipid peroxidation were measured in blood. The study was performed in three stages. For each stage, ten experimental conditions comparing the effect of polyamines with α-tocopherol (10 μM solutions) on LDL oxidation and the uptake of oxLDL by macrophages were analyzed. MDA concentration was found to be significantly higher in type 2 diabetic patients compared to healthy subjects (5.6 ± 0.58 vs. 2.66 ± 0.31 μM MDA, respectively, (P < 0.05)). Percent of macrophages containing oxLDL was determined by means of red oil staining. The uptake of oxLDL by macrophages derived from diabetic patients was clear. The uptake of oxLDL was inhibited when the oxidation was prevented by polyamines or α-tocopherol. Spermine showed high antioxidant capacity (96.67 ± 1.53% vs. 25.67 ± 2.30%) compared to α-tocopherol (96.67 ± 1.53% vs. 47.00 ± 7.20%) at the concentration tested.In conclusion, polyamines especially spermine, has a potent antioxidant effect compared to α-tocopherol on human LDL oxidation, followed by spermidine and putrescine. The results have clinical relevance in the diabetic complications and add knowledge on the role of polyamines as natural antioxidants. This research is not a clinical evaluation rather a functional analysis utilizing clinical samples.     

糖尿病患者血清低密度脂蛋白亚组分的分布及氧化易感性

为探讨糖尿病（ＤＭ）患者血浆低密度脂蛋白（ＬＤＬ）亚组分的异常特性。本文采用密度工超速离心直接分离ＬＤＬ亚组分,并对其分布及体外铜离子介导的氧化易感性进行分析。结果表示单纯ＤＭ患者、ＤＭ合并症患者及对照组间ＬＤＬ亚组分分布无差别;ＤＭ患者ＬＤＬ各组分氧化延滞时间显著缩短,尤以ＤＭ合并症患者明显,示其易于氧化,血浆脂质巡氧化程度亦增高。认为ＤＭ患者动脉粥样硬化的高发生率同其ＬＤＬ易于氧化的我相关联。     

Serum lipid metabolism abnormalities and change in lipoprotein contents in patients with advanced-stage renal disease.

BACKGROUND: Arteriosclerosis is the major cause of death in patients with chronic renal failure. There is much interest in the lipid metabolism of patients treated with hemodialysis. METHODS: We analyzed low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in chronic renal failure (CRF) patients according to patients on hemodialysis (HD), patients with diabetic nephropathy before initiation of dialysis (DN), and patients with chronic glomerulonephritis in the conservative stage (CGN); and compared the lipid metabolic abnormalities in patients on hemodialysis and those not yet on hemodialysis. We also analyzed the qualitative abnormalities of LDL and HDL and their relationship with the pathological stages. RESULTS: Electrophoretic patterns identified small LDL particles and small HDL particles in the three groups, and the degree of denaturation was more enhanced in CRF patients in the conservative stage than in HD patients. For LDL susceptibility to oxidation LDL (oxLDL) by addition of Cu(2+), the lag time was approximately 57 min in healthy controls and CGN patients, but was prolonged to approximately 75 min in HD and DN patients. For HDL susceptibility to oxidation HDL (oxHDL), HD, DN and CGN patients showed lag times shorter than those found in healthy control subjects. These results showed that LDL and HDL in the serum of CRF patients were in a state of enhanced susceptibility to oxidative modification. In Western blot analysis using anti-human-denatured LDL and anti-human-oxidized HDL monoclonal antibodies, bands of low molecular oxLDL at 150-197 kDa were detected in all CRF patients, with marked tailing in CGN patients. Similarly, bands of small oxHDL particles at 110 and 120 kDa were found in HD, DN and CGN patients. CONCLUSIONS: Oxidative modification of both LDL and HDL occurs in patients with advanced CRF resulting in small lipoproteins. Increased production of oxLDL and oxHDL is the main cause of lipid metabolic abnormality in CRF patients.     

Enhanced susceptibility to oxidation and diminished vitamin E content of LDL from patients with stable coronary artery disease.

BACKGROUND: Convincing evidence points to oxidative modification of LDL as an important trigger in a complex chain of events leading to atherosclerosis. We investigated the occurrence of enhanced susceptibility of LDL to oxidation and decreased vitamin E concentration in LDL as additional risk factors promoting atherosclerosis among patients with established coronary artery disease (CAD). METHODS: We examined 132 patients with angiographically confirmed CAD and compared them with 111 healthy control individuals. We measured conjugated diene production to assess susceptibility of LDL to copper-mediated oxidation. Vitamin E content of LDL was measured by HPLC. RESULTS: The mean lag time of LDL oxidation and LDL alpha-tocopherol/LDL-cholesterol ratio were lower in the patients with CAD (55 +/- 14 min and 2.4 +/- 1.0 mmol/mmol) than in the controls (63 +/- 13 min and 2.9 +/- 1.1 mmol/mmol; P <0.0001 and <0.001, respectively). Multiple stepwise regression analysis demonstrated the lag time (odds ratio, 1.96; 95% confidence interval, 1.34-2.87; P <0.0001) and concentration of vitamin E in LDL (odds ratio, 1.65; 95% confidence interval, 1.16-2.33; P <0.005) as independent determinants of CAD. Significant inverse Spearman rank correlations were found between lag time (r = -0.285; P <0.001) or concentration of vitamin E in LDL (r = -0.197; P <0.002) and severity of CAD. Lag times were not significantly correlated with serum C-reactive protein or ferritin. CONCLUSIONS: Our data suggest that a short LDL oxidation lag time and a low concentration of vitamin E in LDL might be independent coronary risk factors for stable CAD in Iranian people.     

Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients

BACKGROUND: Oxidative stress in diabetes increases lipid peroxidation, which stimulates the development of atherosclerosis. METHODS: We investigated in a 3-month placebo-controlled study with 19 normocholesterolemic type 2 diabetic patients whether treatment with 10-mg atorvastatin influenced antioxidants and reduced LDL oxidizability, assessed by in vitro production of conjugated dienes after copper-induced LDL oxidation. RESULTS: The lag phase, as a measure of the resistance of LDL to oxidation, did not change (62.8+/-8.2 respectively 59.6+/-9.7 min, p=n.s.), while conjugated dienes decreased (512+/-74 respectively 487+/-50 nmol, p=0.012). Plasma alpha-tocopherol and ubiquinol levels decreased, while their ratios to LDL cholesterol remained stable. CONCLUSIONS: Atorvastatin favourably influences some parameters of LDL oxidation. Whether this effect is clinically relevant remains to be determined.     

Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant-antioxidant system in patients with psoriasis

BACKGROUND: Psoriasis is a common chronic and recurrent inflammatory skin disease that can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism, and has been associated with increased frequency of cardiovascular events. The current study was designed to evaluate plasma lipids, susceptibility of LDL to oxidation and oxidant-antioxidant status and their relationships in patients with psoriasis. METHODS: The study group included 35 patients with psoriasis (18 females and 17 males), and 35 sex- and age-matched healthy volunteers (16 females and 19 males). From blood samples, their lipids, lipoproteins, acute phase reactants, lipid peroxidation products [lipid hydroperoxide (LHP) and malondialdehyde (MDA)], antioxidant enzymes [glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT)], total antioxidant status (TAS) and autoantibodies against oxidized low-density lipoprotein (AuAb-oxLDL) levels were determined. Moreover, the susceptibility of copper-induced in vitro oxidation of LDL was examined. RESULTS: The mean levels of atherogenic lipids (total cholesterol [TC], triacylglycerol [TG] and LDL cholesterol [LDL-C]), acute-phase reactants (CRP, ESR, PMNLs, ceruloplasmin and fibrinogen) and lipid peroxidation products, AuAb-oxLDL levels in patients with psoriasis were found to be significantly higher than those of healthy subjects. On the other hand, TAS and antioxidant enzyme activities (CAT, SOD and GSH-Px in erythrocyte and SOD in plasma) were significantly lower when compared to healthy subjects. The lag times [t(lag)], a measure of resistance to oxidation of LDL, were also lower. The levels of AuAb-oxLDL in patients were correlated with TC, LDL-C, plasma LHP, erythrocyte MDA, oxidized LDL-MDA (oxLDL-MDA), fibrinogen, CRP, PMNL levels and plasma SOD activities (r = 0.69, P < 0.01; r = 0.64, P < 0.01; r = 0.38, P < 0.05; r = 0.65, P < 0.01; r = 0.34, P < 0.05; r = 0.34, P < 0.05; r = 0.53, P < 0.01, r = 0.34, P < 0.05; r = -0.67, P < 0.01, respectively). On the other hand, t(lag) was correlated negatively with the levels of VLDL-TG, VLDL-TC and LDL-TG but positively correlated with the levels of TAS in psoriatics (r = -0.49, P < 0.01; r = -0.49, P < 0.01, r = -0.65, P < 0.05; r = 0.37, P < 0.05). CONCLUSIONS: It was concluded that the psoriatic patients could be considered as a group with an increased atherosclerotic risk because of increased oxidant stress, decreased antioxidant capacity and susceptibility in lipid profile and lipoprotein content to atherogenicity.     

Plasma lipid oxidation and susceptibility of low-density lipoproteins to oxidation in male patients with stable coronary artery disease

Objectives: Oxidative modifications of low-density lipoproteins (LDL) are considered to be important in the pathogenesis of atherosclerosis. However, the data on the association between LDL oxidation and severity of clinical manifestations of coronary artery disease (CAD) are contradictory. Previous reports were concerned mostly with unstable angina patients. The present study was undertaken to evaluate plasma lipid oxidation status in patients with stable CAD.

Design and Methods: 37 male patients with angiographically confirmed CAD (asymptomatic or suffering from stable angina pectoris) and 32 control subjects were used in the study. Plasma levels of vitamin E and products of lipid peroxidation, as well as parameters of the test for oxidizability of LDL in vitro were measured.

Results: We did not find differences between 2 groups of individuals regarding the levels of products of lipid peroxidation, vitamin E levels, lag time, maximal rate of oxidation, and total amount of conjugated dienes in the test for oxidizability of LDL.

Conclusion: The results of our study challenge, but do not disprove, the oxidative hypothesis of atherosclerosis. Real atherosclerotic modifications of plasma LDL occur apparently in the vascular wall after trapping of LDL by the interstitial matrix. The rise in oxidative parameters in unstable angina reported in the literature may not be the cause of the disease but, rather, the consequence of the multiple brief episodes of ischemia-reperfusion.     

Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopherol into lipoproteins secreted by the liver.

Plasma and lipoprotein alpha-tocopherol concentrations of four patients with familial isolated vitamin E deficiency and six control subjects were observed for 4 d after an oral dose (approximately 15 mg) of RRR-alpha-tocopheryl acetate labeled with six deuterium atoms (d6-tocopherol). Chylomicron d6-tocopherol concentrations were similar in the two groups. d6-Tocopherol concentrations of plasma, very low (VLDL), low (LDL), and high (HDL) density lipoproteins were similar in the two groups only during the first 12 h; then these were significantly lower, and the rate of disappearance faster, in the patients. The times (tmax) of the maximum chylomicron d6-tocopherol concentrations were similar for the two groups, but tmax values in the controls increased in the order: chylomicrons less than VLDL less than or equal to LDL approximately HDL, while the corresponding values in the patients were similar to the chylomicron tmax. Thus, plasma d6-tocopherol in controls increased during chylomicron and VLDL catabolism, whereas in patients it increased only during chylomicron catabolism, thereby resulting in a premature and faster decline in the plasma tocopherol concentration due to a lack of d6-tocopherol secretion from the liver. We suggest that these patients are lacking or have a defective liver "tocopherol binding protein" that incorporates alpha-tocopherol into nascent VLDL.     

The evaluation of autoantibodies against oxidatively modified low-density lipoprotein (LDL), susceptibility of LDL to oxidation,serum lipids and lipid hydroperoxide levels,total antioxidant status,antioxidant enzyme activities,and endothelial dysfunction in patients with Behçet's disease

OBJECTIVES: Beh?et's disease is a multisystem disorder characterized by a chronic inflammation including acute attacks and remission periods. Decreased enzyme activity of the antioxidant system and increased levels of free radicals may have important roles in the damage of tissues observed in the disease period. In addition, the atherogenic tendency of serum lipid, lipoproteins, lipid peroxidation levels and endothelial dysfunction accompany the above mentioned findings. As a consequence of these events, different degrees of low density lipoprotein (LDL) oxidation occur in vivo, and then autoantibodies against oxidized-LDL(AuAb-oxLDL) are produced. DESIGN AND METHODS: Lipids, lipoproteins, lipid hydroperoxide, AuAb-oxLDL, total antioxidant status (TAS), serum-soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1) levels in serum, the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma, were determined in 25 patients with Beh?et's disease and in 25 healthy volunteers. Also, susceptibility to copper-induced in vitro oxidation of LDL by using lag time, a measure of resistance to oxidation, oxidation rate and extent of oxidation, a measure of diene production in both groups, was studied. RESULTS: It was observed that lipid hydroperoxide and AuAb-oxLDL levels in patients with Beh?et's disease were significantly higher, but erythrocyte SOD, CAT, plasma GSH-Px activities, and TAS were significantly lower than those in healthy subjects. Susceptibility of LDL to oxidation in the patients was found to be increased. Total cholesterol, LDL-C and apo B levels and acute phase reactants were significantly higher, but HDL-C and apo AI levels were significantly lower, in patients when compared to healthy subjects. The levels of AuAb-oxLDL in patients were found to correlate with TAS, total cholesterol, LDL-C, lipid hydroperoxide and erythrocyte SOD activities (r = -0.62, p < 0.01; r = 0.64, p < 0.01; r = 0.55, p < 0.01; r = 0.81, p < 0.01; r = -0.63, p < 0.01, respectively). In addition, lipid hydroperoxide levels were found to correlate with total cholesterol, LDL-C and erythrocyte SOD activities (r = 0.45, p < 0.05; r = 0.45, p < 0.05; r = -0.46, p < 0.05, respectively). PAI-1 and sICAM-1 were found to be increased in the patients and correlated with AuAb-oxLDL and lipid hydroperoxide levels (r = 0.56, p < 0.01; r = 0.67, p < 0.01 and r = 0.59, p < 0.01; r = 0.61, p < 0.01, respectively). CONCLUSIONS: It was concluded that the observed increase of lipid, lipoproteins, lipid hydroperoxide, susceptibility of LDL to oxidation, autoantibodies against ox-LDL levels and decrease of antioxidant enzyme activities and total antioxidant status and increased secretion of endothelial derivated peptides including sICAM and PAI-1, and their interactions may indicate that there is a tendency to atherothrombotic events in patients with Beh?et's disease.     

LDL oxidation is associated with increased blood hemoglobin A1c levels in diabetic patients

AIM: To investigate whether levels of blood HbA1c in diabetic patients are associated with susceptibility of LDL to oxidation. METHODS: LDL was separated from blood of 40 diabetic patients with known blood glucose and HbA1c levels. The tendency to undergo lipid peroxidation was assessed via lag time required for initiation of LDL oxidation. HbA1c formation was measured in vitro following incubation of red blood cell (RBC) hemolysate for 3 months with increasing concentrations of glucose in the absence or presence of LDL or oxidized LDL. RESULTS: Lag time for copper-induced LDL oxidation was twice as long in normal subjects compared to diabetic patients. Correlation analyses between LDL oxidation lag time and HbA1c blood levels revealed an R value of 0.74. Incubation of RBC hemolysate with high glucose concentration (up to 400 mg/dl) resulted in increased blood HbA1c concentration by up to 107%. Addition of LDL to this hemolysate over a period of 3 months resulted in LDL oxidation and an increase in HbA1c levels by up to 168%. Similarly, addition of oxidized LDL to the hemolysate increased HbA1c by up to 240%. CONCLUSIONS: Increased tendency of LDL to undergo lipid peroxidation in diabetic patients contributes to increased levels of blood HbA1c, mainly in those with HbA1c<7.3.     

Increased levels of markers of vascular inflammation in patients with coronary heart disease

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor &#102 (TNF &#102 ), interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all < 0.001). In multivariate analysis sVCAM-1 was predicted by age (p = 0.015), sICAM-1 by smoking (p < 0.001) and total cholesterol (p = 0.026), E-selectin by body mass index (BMI) (p = 0.004) and P-selectin by male gender (p = 0.015). TNF &#102 significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNF &#102, but not IL-6, plays a major role in the regulation of sCAM levels in vivo .     

Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes

OBJECTIVE: To compare the effects of short-term dietary supplementation with tomato juice, vitamin E, and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein (C-RP) and cell adhesion molecules in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 57 patients with well-controlled type 2 diabetes aged <75 years treated with placebo for 4 weeks and then randomized to receive tomato juice (500 ml/day), vitamin E (800 U/day), vitamin C (500 mg/day), or continued placebo treatment for 4 weeks. Susceptibility of LDL to oxidation (lag time) and plasma concentrations of lycopene, vitamin E, vitamin C, C-RP, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 were measured at the beginning of the study, after the placebo phase, and at the end of the study. RESULTS: Plasma lycopene levels increased nearly 3-fold (P = 0.001), and the lag time in isolated LDL oxidation by copper ions increased by 42% (P = 0.001) in patients during supplementation with tomato juice. The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E (54%). Plasma C-RP levels decreased significantly (-49%, P = 0.004) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study. CONCLUSIONS: This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E, which also decreases plasma levels of C-RP, a risk factor for myocardial infarction, in patients with diabetes. These findings may be relevant to strategies aimed at reducing risk of myocardial infarction in patients with diabetes.     

Low-density lipoprotein susceptibility to oxidation and cytotoxicity to endothelium in sickle cell anemia.

Patients with sickle-cell anemia exhibit pro-oxidative metabolic perturbations. We hypothesize that because of chronic oxidative stress, plasma low-density lipoprotein (LDL) from patients with sickle-cell anemia is more susceptible to oxidation. To test this hypothesis, LDL susceptibility to copper-mediated oxidation was measured in 24 patients with sickle-cell anemia and 48 control subjects. Sickle-cell LDL was more susceptible to oxidation than control LDL, measured by a 22% shorter mean lag time between LDL exposure to CuSO4 and conjugated diene formation (97 vs 124 minutes; P = .023). LDL vitamin E, iron, heme, and cholesterol ester hydroperoxide (CEOOH) levels were also measured. LDL vitamin E levels were significantly lower in patients with sickle-cell anemia compared with control subjects (1.8 vs 2.9 mol/mol LDL; P = .025), but there was no correlation with lag time. Pro-oxidant heme and iron levels were the same in sickle-cell and control LDL. LDL CEOOHs were not significantly different in sickle and control LDL (3.1 vs 1.2 mmol/mol of LDL unesterified cholesterol, P = .15), but LDL CEOOH levels were inversely correlated with lag times in patients with sickle-cell anemia (r2 = 0.38; P = .018). The cytotoxicity of partially oxidized LDL to porcine aortic endothelial cells was inversely correlated with lag times (r2 = 0.48; P = .001). These preliminary data suggest that increased LDL susceptibility to oxidation could be a marker of oxidant stress and vasculopathy in patients with sickle-cell anemia.     

Effect of Soybean Hypocotyl Extract on Lipid Peroxidation in GK Rats

Vascular complications, as a consequence of atherosclerosis, are main causes of morbidity and mortality in patients with diabetes mellitus. There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. In this study we investigated the effect of soybean hypocotyl extract (SHE), rich in isoflavones and saponins, on lipid peroxide (LPO) levels in liver, plasma and lipoproteins in GK diabetic rats, and its efficacy on the reduction of susceptibility of LDL and high density lipoprotein (HDL) to oxidation. The oxidative modification of LDL and HDL was determined with the lag time of copper ion-induced oxidation curve identified by the conjugated dienes. In SHE group which were fed diet containing 40 g/kg of SHE for 16 weeks, LPO levels in liver, plasma and HDL fraction were significantly decreased compared with the control group. The lag phage of LDL oxidation curve was prolonged noticeably by a mean of 27 min in SHE group as compared to the control group, indicating a reduced susceptibility to oxidation. The results suggest that intake of soybean hypocotyl extract might be useful for the prevention and treatment of diabetes mellitus and diabetes-associated diseases.     

心肌梗死患者血清脂蛋白氧化易感性及高密度脂蛋白氧化抑制能力分析

目的 了解心肌梗死存活患者（MIS）血清脂蛋白氧化易感性以及高密度脂蛋白（HDL）对低密度脂蛋白（LDL）氧化抑制能力的变化。方法 采用密度梯度超了心分离33例MIS患者的血清脂蛋白组分（VLDL，LDL，HDL），用A234nm光吸收鉴定脂蛋白氧化易感性，硫代巴比妥酸值（TBARS）分析脂蛋白脂质过氧化程度，并与正常人（44例）进行了比较，结果 MIS患者VLDL、LDL组分脂质过氧化程度明显高于正常人（P＜0.01），氧化延滞时间明显缩短（P＜0.001），HDL组分对LDL氧化抑制能力显著降低（P＜0.01）。结论 MIS患者VLDL，LDL组分氧化易感怀增加，HDL抗氧化能力受损，可能与其动脉粥样硬化的发生发展有关。     

Exhaustive exercise increases plasma/serum total oxidation resistance in moderately trained men and women,whereas their VLDL + LDL lipoprotein fraction is more susceptible to oxidation

The purpose of this study was to evaluate the effects of exhaustive exercise (marathon run) on different lipid peroxidation measurements, including copper-induced serum lipids and VLDL + LDL oxidation susceptibility, and on plasma total antioxidative capacity (TRAP), muscular damage and plasma antioxidants in healthy moderately trained male (n = 21) and female (n = 25) volunteers. Blood samples were taken before and just after the 42-km run. In women, baseline levels of several antioxidative compounds (serum albumin and uric acid, plasma free thiols and blood glutathione) were lower, resulting in 21.5% lower plasma total antioxidative capacity and 70.3% higher serum oxidation susceptibility, compared to men. To compare effects in men and women, the exercise-induced variable changes were adjusted for their baseline levels. After this adjustment, there were no statistically significant differences between the genders in the extent of muscular damage (serum creatine kinase, (CK)), or in the change in serum lipids or VLDL + LDL oxidation susceptibility, or that of plasma antioxidative capacity. A possible beneficial effect of exercise was that serum HDL cholesterol levels increased significantly in both genders, but especially in women. In the group of pooled genders (n=46), the increases in serum CK and in plasma lactate were 190% (95% CI, 133% to 246%) and 109% (95% CI, 65% to 175%), respectively. On the basis of our lipid peroxidation and TRAP measurements, uric acid was observed to be the most important plasma antioxidant. The effect of exercise was to decrease the oxidation susceptibility of serum lipids by 24.8% (95% CI 13.4% to 36.2%) and to elevate plasma TRAP by 14.6% (95% CI, 11.4% to 17.7%). Nonetheless, the oxidation susceptibility of the VLDL + LDL fraction increased by 11.0% (95% CI, 1.9% to 20.2%). Our results suggest that there are no gender-based differences in exhaustive exercise-induced lipid peroxidation or muscular damage. Secondly, even though exhaustive exercise can increase plasma/serum total resistance towards oxidation, the oxidation resistance of the atherogenic lipoprotein fraction might be diminished. On the basis of these results, several in vitro measurements of lipid peroxidation assessing both water and lipid soluble plasma fractions are needed if a true perspective of the plasma redox status is to be obtained.