Oxidized LDL Concentrations Research Articles

Effect of the anti-oxidant probucol on soluble thrombomodulin (sTM) in hypercholesterolemic rabbits

Introduction Thrombomodulin is an integral endothelial cell membrane protein, exists not only on the surface of endothelial cells but also as soluble fragments circulating in plasma. Probucol has anti-oxidant properties as well as cholesterol-lowering effects and may affect soluble thrombomodulin (sTM). Methods Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (1) high-cholesterol group ( n = 8): maintained high-cholesterol diet; (2) probucol group (n = 8): the same diet plus probucol for 6 weeks. Control group ( n = 8) was fed with normal diet for 14 weeks. The levels of sTM and oxidized low-density lipoprotein (OX-LDL) were measured using ELISA. Results There were atherosclerotic lesions in aortas and intimal thickness significantly increased in high-cholesterol group. Probucol significantly reduced the lesion area (56.4% ± 9.8% vs 82.5% ± 10.5%) and decreased the intimal thickness (44.65 ± 7.25 μm vs 72.21 ± 8.32) as compared with high-cholesterol group, all P < 0.01. Probucol decreased the level of OX-LDL and sTM as compared with high-cholesterol group, all P < 0.05. Conclusions Probucol retarded the plaques formation may relate to decrease plasma OX-LDL and sTM concentration, which may improve endothelial function in hypercholesterolemic rabbit.

Tea Catechin Consumption Reduces Circulating Oxidized Low-Density Lipoprotein

It has been reported that green tea consumption reduces the risk of coronary artery disease and cardiac events. Catechin is a major constituent of Japanese green tea and an antioxidant. Lipids and oxidization of low-density lipoprotein cholesterol (LDL-C) play important roles in atherosclerosis. Therefore, we evaluated the effect of catechin intake on the lipid profile and plasma oxidized LDL. The study population consisted of 40 healthy adult volunteers (10 men, 30 women). Catechin was extracted from green tea leaves. The subjects were randomly divided into two groups, a catechin group (n = 29) and a control group (n = 11). In the catechin group, catechin (500 mg: equivalent to 6 or 7 cups of green tea) was administered orally. Venous blood samples were obtained before eating a meal at the start and after 4 weeks without any lifestyle modification. Plasma oxidized LDL assay was performed with a sandwich-type enzyme immunoassay using anti-oxidized phosphatidylcholine monoclonal antibody. The baseline lipid profiles and tea consumptions were similar between the two groups. Plasma oxidized LDL was significantly decreased after catechin administration (from 9.56 +/- 9.2 to 7.76 +/- 7.7 U/mL, P = 0.005), while plasma LDL-C, triglyceride, and HDL-C concentrations did not change. Catechin decreased the plasma oxidized LDL concentration without significant change in plasma LDL concentration. The mechanism of the beneficial effects of green tea on coronary artery disease might result from a decrease in plasma oxidized LDL.

Effect of insulin treatment on plasma oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients

In type 2 diabetes mellitus, oxidized LDL/LDL-Cholesterol ratio, an accurate estimation of in vivo LDL oxidation, has been reported elevated and associated with macrovascular disease. Because insulin therapy induces significant modification of lipid metabolism, in type 2 diabetes, we evaluated the effect of insulin treatment on oxidized LDL/LDL-C ratio in type 2 diabetic patients and analyzed the results in comparison with the modifications induced by insulin on glycaemia, plasma lipids and LDL receptors. Plasma oxidized LDL concentrations were measured by sandwich ELISA in 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy, and in 27 age-matched controls. Type 2 diabetic patients had, compared to controls, significantly increased oxidized LDL/LDL-C ratio (P<0.0001). Three months after insulin treatment, oxidized LDL/LDL-C ratio was significantly reduced (21.1+/-4.7 vs. 24.0+/-5.8 U/mmol, P<0.01). This reduction was strongly associated, in multivariate analysis, with reduction of LDL(TG/cholesterol ratio) (P=0.008), and to a lesser extent with the decrease of LDL fructosamine (P=0.034), but not with the increase of the number of LDL receptors. In the present study we demonstrate for the first time a lowering effect of insulin therapy on oxidized LDL/LDL-C ratio in type 2 diabetic patients. This decrease is mainly associated with the reduction of LDL TG-enrichment, and to a lesser extent with the decrease of LDL glycation, but not with the insulin-induced increase in number of LDL receptors.

Defective Metabolism of Oxidized Phospholipid by HDL From People With Type 2 Diabetes

HDL protects against atherosclerosis development. Defective functioning of HDL in type 2 diabetes may be one cause of increased cardiovascular disease associated with type 2 diabetes. HDL modulates LDL oxidation through the action of paraoxonase-1 (PON1), which is one of the major mechanisms by which HDL is antiatherogenic. We have compared the ability of HDL from people with type 2 diabetes (n = 36) with no coronary heart disease (CHD) to metabolize oxidized palmitoyl arachidonyl phosphatidylcholine (ox-PAPC), a major product of LDL oxidation and a PON1 substrate, with that of HDL isolated from healthy control subjects (n = 19) and people with CHD but no diabetes (n = 37). HDL from people with type 2 diabetes metabolized 11% less ox-PAPC, and HDL from people with CHD metabolized 6% less, compared with HDL from control subjects (both P < 0.01). The ability of HDL from control and type 2 diabetic subjects containing the PON1-192RR alloform to metabolize ox-PAPC was significantly reduced compared with PON1-192QQ or QR genotypes (P < 0.05). The defective ability of HDL to metabolize ox-PAPC was reflected in a significant increase in circulating plasma oxidized LDL concentration in the two patient groups (37 +/- 5, 53 +/- 7, and 65 +/- 7 mmol/l for control, CHD, and type 2 diabetic subjects, respectively; P < 0.001), with PON1-192RR genotype carriers having the highest concentrations. In the control group, there was a significant negative correlation between serum PON1 activity and oxidized LDL concentration (r = 0.856, P < 0.001); however, this correlation was not evident in the patient groups. HDL from type 2 diabetic subjects without CHD had a decreased ability to metabolize oxidized phospholipids, which could lead to increased susceptibility to develop cardiovascular disease.

OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages

Oxidized low density lipoprotein (OxLDL) is immunogenic and induces autoimmune responses in humans. OxLDL antibodies are predominantly of the proinflammatory IgG1 and IgG3 isotypes. We tested the capacity of immune complexes prepared with copper-oxidized human LDL and affinity chromatography-purified human OxLDL antibodies [OxLDL-immune complexes (ICs)] to activate complement and to induce cytokine release by MonoMac 6 (MM6) cells and by primary human macrophages. The levels of C4d and C3a were significantly higher in human serum incubated with OxLDL-ICs than after incubation with OxLDL or OxLDL antibody, indicating complement activation by the classical pathway. MM6 cells and primary human macrophages were incubated with OxLDL-ICs, with or without prior conditioning with interferon-gamma. After 18 h of incubation, both MM6 cells and primary human macrophages released significantly higher levels of proinflammatory cytokines after incubation with OxLDL-ICs than after incubation with OxLDL or with OxLDL antibody, both in primed and unprimed cells. OxLDL-ICs were more potent activators of MM6 cells than keyhole limpet hemocyanin-ICs. Blocking Fc gamma receptor I (FcgammaRI) with monomeric IgG1 significantly depressed the response of MM6 cells to OxLDL-ICs. In conclusion, human OxLDL-ICs have proinflammatory properties, as reflected by their capacity to activate the classical pathway of complement and to induce proinflammatory cytokine release from MM6 cells and primary human macrophages.

Effect of a polyphenoics extracts of Grape Seeds (GSE) on Blood Pressure(BP) in patients with the Metabolic Syndrome (MetS)

Effect of a polyphenoics extracts of Grape Seeds (GSE) on Blood Pressure(BP) in patients with the Metabolic Polyphenolic compounds in grape seeds are potent anti-oxidants which cause a NO mediated endothelium dependent relaxation of blood vessels. The present study was undertaken to determine whether a GSE lowers BP in subjects with the MetS . The GSEs which was manufactured by Polyphenolics Inc. (Madera, CA) contains ~95% phenolic compounds and is low gallate units. 24 subjects with MetS (NCEP III) were randomized into 3 groups (n=8) and given either a placebo, 150 mg/day or 300 mg/day of the extract. A 12 hour ambulatory BP recording was made at the start of the study and after 4 weeks of treatment. Serum lipids, blood glucose, plasma insulin and oxidized LDL were measured at the start and end of the study. Oxidized LDL was measured using an ELISA (Mercodia Inc, Uppsala, Sweden). After 4 weeks subjects receiving both 150 mg and 300 mg of GSEs significantly lowered their BP while those on placebo showed no significant change (p < 0.05, ANOVA). The fasting blood glucose, plasma insulin, serum lipids and plasma oxidized LDL concentrations were unchanged. Insulin resistance as determined by the homeostasis model was elevated in all 3 groups but did not change with treatment. It is suggested that the GSE used in the present study which has been granted GRAS status by the FDA, is a potentially useful nutraceutical compound for the management of BP in patients with Met S.

Oxidized low-density lipoprotein (Oxidized LDL) and the risk of preeclampsia

Oxidative stress plays an important role in the pathophysiology of preeclampsia. In a case-control study of 99 women with preeclampsia and 99 controls, we assessed maternal plasma oxidized low-density lipoprotein (oxidized LDL) in relation to preeclampsia risk. Logistic regression procedures were used to derive odds ratios (OR) and 95 % confidence intervals (CI). Plasma oxidized LDL was determined using enzyme immunoassay. Maternal plasma oxidized LDL was significantly positively correlated with lipids in both cases and controls. After adjusting for nulliparity, pre-pregnancy body mass index, physical inactivity, family history of chronic hypertension and plasma vitamin C concentrations, women who had elevated oxidized LDL concentrations ( > or = 50 U/l) experienced a 2.9-fold increased risk of preeclampsia when compared with women having lower oxidized LDL concentrations (95 % CI 1.4-5.9). The risk of preeclampsia was markedly increased in women who had both elevated oxidized LDL and elevated triglyceride concentrations (OR=8.9, 95 % CI 3.1-26.2). Women with both elevated oxidized LDL and low vitamin C concentrations experienced a 9.8-fold increased risk of preeclampsia (95 % CI 3.0-32.2). Our results confirm the role of oxidative stress in the pathogenesis of preeclampsia. Prospective studies are needed to determine if elevated oxidized LDL concentrations can predict the occurrence of preeclampsia.

Circulating Levels of Oxidative Stress Markers and Endothelial Adhesion Molecules in Men with Abdominal Obesity

It has been suggested that oxidative stress and endothelial dysfunction could play a role in the higher cardiovascular disease risk noted in the abdominally obese population. The objective of this study was to describe the associations between abdominal fat accumulation, oxidative stress, and endothelial dysfunction in men. A complete physical and metabolic profile was assessed in a group of 56 men covering a wide range of adiposity and plasma oxidized low-density lipoprotein (OxLDL), and soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and C-reactive protein concentrations were determined. We found that abdominal visceral adipose tissue was positively associated with plasma OxLDL (r = 0.52; P < 0.0001) and C-reactive protein (r = 0.60; P < 0.0001) concentrations. We also found significant associations between plasma E-selectin levels and hyperinsulinemia (r = 0.39; P < 0.005) as well as with the homeostasis model assessment index of insulin resistance (r = 0.42; P < 0.005). Our study showed that plasma OxLDL levels and low-grade systemic inflammation are increased in men with a high visceral adipose tissue accumulation. Furthermore, our results support the notion that insulin resistance is associated with endothelial activation. Overall, our observations give us further insights on the increased cardiovascular disease risk frequently noted among viscerally obese, insulin-resistant individuals.

Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption

Low-density lipoprotein (LDL) oxidation is closely implicated in the development of atherosclerotic cardiovascular disease (CVD), and thus, reducing LDL susceptibility to oxidation with antoxidants could be of importance in CVD prevention. Flavonoids, polyphenolic compounds found in a large selection of fruits and vegetables, have been characterized as having a strong antioxidant potential, and intake of flavonoid-rich foods has been related to decreased morbidity and mortality from heart disease. The present study was therefore undertaken to investigate the effect of flavonoid-rich cranberry juice supplementation on plasma lipoprotein levels and LDL oxidation. For that purpose, 21 men (age ± SD, 38 ± 8 years) were enrolled in a 14-day intervention and instructed to drink cranberry juice 7 mL/kg body weight per day. Physical and metabolic measures including plasma lipid and oxidized LDL (OxLDL) concentrations as well as antioxidant capacity were performed before and after the intervention. At baseline, we found that plasma OxLDL levels were significantly associated with waist circumference ( r = 0.47, P = .0296) as well as plasma triglyceride ( r = 0.68, P = .0007) and apolipoprotein B ( r = 0.91, P < .0001) concentrations. The intervention led to a reduction in plasma OxLDL levels (−9.9% ± 17.8%, P = .0131) and increase in antioxidant capacity (+6.5% ± 10.3%, P = .0140). However, no relationship was found between both of these changes ( r = −.01, not significant). The intervention did not result in any improvement of plasma lipoprotein-lipid or inflammatory marker concentrations. Our results show that short-term cranberry juice supplementation is associated with significant increase in plasma antioxidant capacity and reduction in circulating OxLDL concentrations. Although the physiological relevance of our observations needs to be further examined, our study supports the potential role of antioxidant-rich foods in maintaining health and preventing CVD.

Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia

HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL (OxLDL), subclinical inflammation [high-sensitive C-reactive protein (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, -107C/T, -162A/G, -824G/A, and -907G/C) were determined in 302 patients with familial hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were determined using an immunoassay. The genetic variants of PON1 that were associated with high levels and activity of the enzyme were associated with higher HDL-C levels (P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M, Q192R, -107C/T, and -907G/C, respectively). In addition to the PON1 genotype, there was also a positive correlation between PON1 levels and activity and HDL-C (PON1 levels: r = 0.37, P < 0.001; paraoxonase activity: r = 0.23, P = 0.01; diazoxonase activity: r = 0.29, P < 0.001; arylesterase activity: r = 0.19, P = 0.03). Our observations support the hypothesis that both PON1 levels and activity preserve HDL-C in plasma.

A case-control study of oxidized low density lipoproteins and preeclampsia risk

Diffuse vascular endothelial dysfunction, secondary to oxidative stress, is an important pathological feature of preeclampsia. Oxidative conversion of low density lipoproteins (LDL) to oxidized-LDL (Ox-LDL) is considered an important step in transforming macrophages into lipid-laden foam cells destined to develop into early atherosclerotic-like lesions. In our study of 95 women with preeclampsia and 100 controls, we evaluated the association between maternal plasma Ox-LDL concentrations and preeclampsia risk. Ox-LDL concentrations were measured using a solid phase two-site enzyme immunoassay. Plasma lipids were measured using standard enzymatic procedures. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. Plasma Ox-LDL concentrations were positively correlated with cholesterol, triglyceride (TG), and LDL concentrations in cases and controls, (Spearman's r ranging from 0.39–0.48, p-values all <0.01). There was no evidence of an increased risk of preeclampsia across increasing quartiles of Ox-LDL. The ORs for successive quartiles, with the lowest as the reference group, were as follows: 1.0, 1.1, 0.6, and 1.2. Women with extremely high concentrations of Ox-LDL (≥73 U/L, the upper decile), as compared with those with lower values (<73 U/L) had a 2.7-fold increased risk of preeclampsia (95% CI 1.0–6.8). Women with high Ox-LDL and high TG concentrations (≥284 mg/dl), as compared with those without these two factors, had a 9.6-fold increased preeclampsia risk (95% CI 2.0–45.6). Elevated Ox-LDL, particularly in conjunction with elevated TG, appears to be a risk factor of preeclampsia.

Oxidized LDL Induces Proliferation and Hypertrophy in Human Umbilical Vein Endothelial Cells via Regulation of p27Kip1 Expression

Oxidized LDL (OxLDL) induces proliferation in human umbilical vein endothelial cells (HUVEC). The influence of OxLDL on the cyclin-dependent kinase inhibitor p27(Kip1), on the activity of the small GTPase RhoA as a known regulator of p27(Kip1), and on resulting cell proliferation and hypertrophy was studied. HUVEC were stimulated with OxLDL (1 to 50 mug/ml). Proliferation was quantified by (3)H-thymidine incorporation, colorimetric 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2h-tetrazolium bromide assay, and cell count and was compared with proliferation of HUVEC that were transfected with dominant negative RhoA or treated with the Rho-kinase inhibitor Y27632. Hypertrophy was quantified by (3)H-leucine incorporation and by planimetry. p27(Kip1) expression was determined by Western blot analysis. p27(Kip1) was downregulated by transient transfection with antisense oligonucleotides. Low concentrations of OxLDL induced proliferation of HUVEC, paralleled by a persistent decrease of p27(Kip1) expression. With the use of antisense oligonucleotides, further downregulation of p27(Kip1) expression enhanced the OxLDL-induced proliferative response. High concentrations of OxLDL resulted in cellular hypertrophy and caused a delayed increase in p27(Kip1) expression after initial downregulation. Concomitant, OxLDL caused a significant activation of the small GTPase RhoA. In cells that were transfected with dominant negative RhoA, the effect of OxLDL on p27(Kip1) expression and on cellular proliferation was abolished. HUVEC that were preincubated with the Rho-kinase inhibitor Y27632 also showed a significantly decreased proliferative response to OxLDL stimulation. In summary, OxLDL has a dual effect on cell-cycle progression via regulation of p27(Kip1) expression, resulting in cellular proliferation and hypertrophy, involving activation of RhoA. OxLDL may importantly contribute to vascular hyperplasia in atherosclerosis and other diseases associated with increased levels of OxLDL.

Lack of association between oxidized LDL-cholesterol concentrations and haptoglobin phenotypes in healthy subjects

The haptoglobin (Hp) 2-2 phenotype has been known to have less antioxidative activity than Hp 1-1 and Hp 2-1. However, few have reported the relationship between oxidative stress and Hp phenotypes by using oxidized LDL. The relationship between Hp phenotypes and oxidative stress was therefore investigated in healthy adults. The serum Hp concentrations, albumin, uric acid, iron, L-ascorbic acid, total antioxidant status and oxidized LDL concentrations were measured and analysed in 200 healthy Korean men and women with Hp 2-1 and Hp 2-2 phenotypes. The serum concentrations of Hp were significantly higher in the Hp 2-1 compared with the Hp 2-2 phenotype. However, serum concentrations of total antioxidant status and oxidized LDL did not show any statistical differences in either sex. The L-ascorbic acid concentrations in serum showed lower values in the Hp 2-2 compared with the Hp 2-1 phenotype, for both sexes (P < 0.05). The concentration of L-ascorbic acid, the first line antioxidant, was lower in the Hp 2-2 than in the Hp 2-1 phenotype; this did not significantly affect the total antioxidant status, and there was no significant difference in oxidized LDL for either group in healthy adults.

Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men.

To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. Prospective, observational study with more than 3 years of follow-up. One-centre study at university hospital. The subjects (n = 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6. OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P = 0.008), also after adjustment for plaque status at entry (P = 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P = 0.005). These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.

W01.88 Reduction of plasma oxidized LDL concentration but not change of LDL oxidation level following treatment of familial hypercholesterolemia patients with statins

W01.88 Reduction of plasma oxidized LDL concentration but not change of LDL oxidation level following treatment of familial hypercholesterolemia patients with statins

W01.88 Reduction of plasma oxidized LDL concentration but not change of LDL oxidation level following treatment of familial hypercholesterolemia patients with statins

This study was designed to assess the relation between apolipoprotein E (apoE) genotype and serum interleukin (IL)-10 levels in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA).Genetic variations in the apoE gene affect the risk for coronary artery disease (i.e., carriers of the e4 allele have an increased risk). Increased levels of C-reactive protein (CRP), an inflammatory marker, correlate with an increased risk of acute coronary events, whereas increased IL-10 concentrations have an atheroprotective role. Studies have reported a negative association between the apoE e4 allele and CRP levels.Apolipoprotein E genotypes were assessed in 166 consecutive ACS patients (119 men, mean age 68 years, interquartile range [IQR] 60 to 74 years) and 70 CSA patients (54 men, mean age 65 years, IQR 62 to 68 years). Serum IL-10 and CRP were assessed at study entry.Analysis of covariance showed that genetic variation in the apoE gene locus significantly influences serum IL-10 levels in both ACS (p = 0.009) and CSA patients (p = 0.013). Among ACS patients, IL-10 levels were lower in E3/E4 carriers compared with E3/E3 carriers (p = 0.01) and marginally lower compared with E2/E3 carriers (p = 0.065). Among CSA patients, IL-10 levels were lower in E3/E4 carriers compared with E2/E3 carriers (p = 0.004) and marginally lower compared with E3/E3 carriers (p = 0.086).The IL-10 concentrations differ in ACS and in CSA patients with different apoE genotypes. The e4 allele was associated with a trend toward lower IL-10 serum levels. Our results may provide an explanation of findings in previous studies that cardiovascular risk is higher in e4 carriers despite the presence of low CRP levels.

Correlation of plasma oxidized low-density lipoprotein levels to vascular complications and human serum paraoxonase in patients with type 2 diabetes

The oxidative modification of low-density lipoprotein (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and has been shown to reduce the susceptibility of LDL to lipid peroxidation. We investigated whether circulating oxidized LDL (Ox-LDL) levels were associated with diabetic vascular complications, and whether the enzymatic activity and gene polymorphisms of PON1 influenced Ox-LDL concentrations in vivo. There was no difference in the plasma Ox-LDL concentrations between diabetic patients with and without macrovascular diseases. However, Ox-LDL concentrations corrected by LDL-cholesterol (OxLDL/LDL-C) or apolipoprotein B (apoB) concentrations (Ox-LDL/apoB), which probably reflect the proportion of oxidatively modified LDL to total LDL particles, were significantly higher in patients with macrovascular diseases than in those without. In addition, patients with peripheral neuropathy had a significantly higher Ox-LDL/apoB ratio than patients without this complication. The genotype TT of −108C/T polymorphism in the promoter region of the PON1 gene, which is associated with decreased PON1 expression, showed a significantly higher Ox-LDL/apoB ratio than genotypes TC or CC (TT: 0.60 ± 0.15, CT + CC: 0.55 ± 0.11, P = .02). Stepwise multiple regression analysis for Ox-LDL concentration revealed that the −108C/T polymorphism, subsequently to apoB concentration, was identified as a significant contributor. In summary, the Ox-LDL/apoB ratio was associated with macrovascular disease and peripheral neuropathy in Japanese patients with type 2 diabetes. Increased Ox-LDL/apoB may result, at least partly, from reduced serum antioxidant capacity in the diabetic state, including the attenuation of PON1 action. Increased Ox-LDL/apoB could be a significant marker for susceptibility to vascular complications in diabetic patients.

Response of oxidative stress biomarkers to a 16-week aerobic physical activity program, and to acute physical activity, in healthy young men and women

Physical activity (PA) is associated with a reduced risk of coronary heart disease, and may favorably modify the antioxidant–prooxidant balance. This study assessed the effects of aerobic PA training on antioxidant enzyme activity, oxidized LDL concentration, and LDL resistance to oxidation, as well as the effect of acute PA on antioxidant enzyme activity before and after the training period. Seventeen sedentary healthy young men and women were recruited for 16 weeks of training. The activity of superoxide dismutase in erythrocytes (E-SOD), glutathione peroxidase in whole blood (GSH-Px), and glutathione reductase in plasma (P-GR), and the oxidized LDL concentration and LDL composition, diameter, and resistance to oxidation were determined before and after training. Shortly before and after this training period they also performed a bout of aerobic PA for 30 min. The antioxidant enzyme activity was also determined at 0 min, 30 min, 60 min, 120 min, and 24 h after both bouts of PA. Training induces an increase in GSH-Px (27.7%), P-GR (17.6%), and LDL resistance to oxidation, and a decrease in oxidized LDL (−15.9%). After the bout of PA, an increase in E-SOD and GSH-Px was observed at 0 min, with a posterior decrease in enzyme activity until 30–60 min, and a tendency to recover the basal values at 120 min and 24 h. Training did not modify this global response pattern. Regular PA increases endogenous antioxidant activity and LDL resistance to oxidation, and decreases oxidized LDL concentration; 30 min of aerobic PA decreases P-GR and B-GSH-Px activity in the first 30–60 min with a posterior recovery.

4P-0989 The polymorphism in the 3′ untranslated region of IL-12B and plasma oxidized LDL concentrations in type 2 diabetic patients

4P-0989 The polymorphism in the 3′ untranslated region of IL-12B and plasma oxidized LDL concentrations in type 2 diabetic patients

Paraoxonase1-192 polymorphism modulates the effects of regular and acute exercise on paraoxonase1 activity

Regular exercise practise is a protective factor against coronary heart disease and enhances antioxidant systems, whereas acute exercise appears to be a major source of increased oxidative stress. Paraoxonase1 (PON1) is an antioxidant HDL-linked enzyme, whose activity toward paraoxon (PON1 activity) is strongly modulated by the PON1-192 polymorphism, comprising Q and R alleles for low and high PON1 activity, respectively. Another polymorphism at the PON1 locus, the PON1-55, modulates PON1 protein and activity levels. PON1 activity, lipid levels, and oxidized LDL concentration were determined in 17 healthy young volunteers before and after a 16-weeks aerobic exercise training period. Furthermore, PON1 activity was analyzed after a bout of exercise in both situations. We found that regular exercise was associated with a decrease in oxidized LDL levels, and an increase in PON1 activity in QQ subjects and with a decrease in PON1 activity in R carriers. A bout of exercise produced an increase in PON1 activity just after the bout of exercise, followed by a decrease in its activity. A recovery of the basal PON1 activity levels at 24 h was found in QQ subjects regardless of their training status and in trained R carriers, but not in untrained R carriers. These results suggest that the effects of regular and acute exercise on PON1 activity levels are modulated by PON1-192 polymorphism. Changes were less evident for the PON1-55 polymorphism.—Tomás, M., R. Elosua, M. Sentí, L. Molina, J. Vila, R. Anglada, M. Fitó, M. I. Covas, J. Marrugat. PON1-192 polymorphism modulates the effects of regular and acute exercise on paraoxonase1 activity. J. Lipid Res. 2002. 43: 713–720.