Increased low-density lipoprotein oxidation,but not total plasma protein oxidation,in Alzheimer's disease

ObjectivesThe two most common forms of dementia are Alzheimer's disease (AD), and vascular dementia (VaD). In the overlap of biochemical processes which have been identified in AD and VaD, oxidative stress is believed to contribute to the numerous pathologies of both dementias.Design and methodsThis study assessed oxidative damage in total plasma proteins, and isolated LDL in AD patients and age matched controls, in addition total antioxidant capacity (TAC) was measured.ResultsSignificantly higher LDL protein carbonylation was observed in AD compared to age-matched controls (AD: 4.17 ± 0.73 vs. control: 3.85 ± 0.86 nmol/mg LDL; p = 0.05, 2-tailed Mann–Whitney), in addition to reduced TAC (AD: 924.708 ± 174.429 vs. control: 1078.536 ± 252.633 μM; p = 0.001, 2-tailed Mann–Whitney). No differences were seen in total plasma protein carbonyl content (AD: 3.88 ± 0.31 vs. control: 3.98 ± 0.48 nmol/mg protein).ConclusionThe results further support the view that oxidation events in AD may be specific in nature, and represent functional changes to proteins, rather than random global events.     

Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus

Background: Patients with diabetes mellitus have been reported to show increased serum levels of modified low-density lipoprotein (LDL), including glycosylated, oxidized and small, dense LDL. This change has been suggested to represent an important risk factor for diabetic macroangiopathy. A common characteristic shared by these modified LDL species is the increase in electronegative charge on particle surfaces, which can be detected by agarose gel electrophoresis as “LDL charge modified frequency” (LDL-CMF) determined from the relative mobility of LDL fraction. Methods: LDL-CMF was measured in the sera from 129 outpatients with type 2 diabetes mellitus and compared with the data from 34 normal subjects. Results: The LDL fraction from diabetics migrates more closely to the anode side as compared with that from normal subjects. The LDL-CMF measured in diabetics, 5.5±8.1%, was significantly (p<0.0001) higher than 0.6±3.4% in normal subjects. Serum LDL-CMF showed significant positive correlations with triglyceride at r=0.552 (p<0.0001) and malondialdehyde modified LDL at r=0.390 (p<0.0001), as well as systolic blood pressure, body mass index, fasting plasma glucose, hemoglobin A_1c, total cholesterol, free fatty acid (FFA) and homeostasis model assessment ratio. It showed negative correlations with high-density lipoprotein and total superoxide dismutase activity. Conclusion: The results indicate that LDL-CMF reflects the degree of serum LDL modification in diabetics and can be regarded as an important risk factor for diabetic macroangiopathy.     

Increased activity of platelet-activating factor acetylhydrolase in low-density lipoprotein subfractions induces enhanced lysophosphatidylcholine production during oxidation in patients with heterozygous familial hypercholesterolaemia

Patients with heterozygous familial hypercholesterolaemia (FH) have elevated plasma concentrations of low-density lipoprotein (LDL) and develop premature atherosclerosis. There is increasing evidence that oxidative modification of LDL is important for the pathogenesis of atherosclerosis, and the LDL-associated platelet-activating factor acetylhydrolase (PAF-AH) seems to play a key role in LDL oxidation by hydrolysing the oxidized phospholipids of phosphatidylcholine (PC) and producing lysophosphatidylcholine (lyso-PC). We measured the total serum and high-density lipoprotein (HDL) levels of PAF-AH activity and studied the distribution of PAF-AH activity among three LDL subfractions isolated by gradient ultracentrifugation in 15 patients with heterozygous FH and 13 normolipidaemic control subjects. We also determined the lyso-PC production in each LDL subfraction during Cu²⁺-induced oxidation in vitro. The total serum PAF-AH activity in heterozygous FH patients was significantly higher than in control subjects, whereas the HDL-associated PAF-AH activity, expressed as a percentage of total serum PAF-AH activity, was significantly lower in the FH patients than in control subjects (13.9 ± 6.6% vs. 30.6 ± 4.4%, P < 0.001). Among the LDL subfractions, the PAF-AH activity in both normolipidaemic control subjects and FH patients, expressed as nmol mg^?1 protein min^?1, was significantly higher in the LDL3 subfraction (33.1 ± 4.8 and 53.4 ± 11.5 respectively) than in the LDL2 (18.6 ± 5.3 and 26.8 ± 10.4 respectively, P < 0.0001 for both comparisons) and LDL1 subfractions (5.1 ± 1.5 and 7.8 ± 2.6, respectively, P < 0.0001 for both comparisons). Additionally, the enzyme activity in each LDL subfraction of the heterozygous FH patients was significantly higher than in control subjects (P < 0.02 for LDL1, P < 0.03 for LDL2 and P < 0.0001 for LDL3). No difference was observed in the susceptibility to oxidation of each LDL subfraction among the heterozygous FH patients and the normolipidaemic control subjects. During oxidation, the PAF-AH activity decreased, whereas the lyso-PC levels significantly increased in all subfractions of both groups. The lyso-PC/sphingomyelin molar ratio in each LDL subfraction of the FH patients 3 h after the onset of the oxidation was significantly higher than in control subjects [0.38 ± 0.05 and 0.27 ± 0.04, respectively, for LDL1 (P < 0.006), 0.47 ± 0.08 and 0.39 ± 0.03, respectively, for LDL2 (P < 0.04), 0.55 ± 0.11 and 0.42 ± 0.06, respectively, for LDL3 (P < 0.02)]. Our results show that heterozygous FH patients exhibit higher PAF-AH activity than control subjects in all LDL subfractions, resulting in higher lyso-PC production during oxidation, which confers on these subfractions higher biological potency. This phenomenon, in combination with the diminished anti-atherogenic and antioxidant capability of HDL in these patients due to the relatively low HDL-cholesterol levels compared with LDL-cholesterol levels and, consequently, the relatively low HDL-associated PAF-AH activity, could contribute to the higher atherogenicity and incidence of coronary artery disease observed in FH patients.     

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.     

Long chain polyunsaturated fatty acids may account for higher low-density lipoprotein oxidation susceptibility in Lithuanian compared to Swedish men

OBJECTIVES: Mortality in coronary heart disease among middle-aged men is four times higher in Lithuania than in Sweden. Traditional risk factors cannot account for this difference. We earlier reported that low-density lipoprotein (LDL) in Lithuanian men showed a lower resistance to oxidation, measured as LDL lag time during copper oxidation, than that in Swedish men. Serum concentrations of several fat-soluble antioxidant vitamins were lower among Lithuanian men. The aim of this study was to investigate whether differences in LDL fatty acid composition could account for the difference in LDL oxidation susceptibility between men in the two countries. METHODS: This cross-sectional study included randomly selected healthy 50-year-old men from Vilnius, Lithuania (n=50) and Link?ping, Sweden (n=50). Main outcome measures were fatty acids in LDL, phospholipid (PL) and cholesterol ester (CE) fractions of LDL and LDL oxidation susceptibility. RESULTS: The mean proportions of PL 20:5n3 (eicosapentaenoic acid, EPA) were higher in Vilnius men (2.09 +/- 1.05 vs. 1.53 +/- 0.58%, p= 0.004). LDL lag time was shorter in Vilnius men, mean +/- SD (75.4 +/- 13.6 vs. 89.5 +/- 13.1 mins, p<0.0001) than in Link?ping men. Mean serum gamma-tocopherol was lower in Vilnius men (0.07 +/- 0.05 vs. 0.12 +/- 0.04 microg/mmol, p<0.0001) but alpha-tocopherol did not differ. In a multiple regression analysis controlled for city, high PL-EPA, low alpha-tocopherol, and high plasma triglycerides significantly contributed to a short LDL lag time, r2=0.53. CONCLUSIONS: Fat quality, i.e. poly unsaturated fatty acids, especially LDL-EPA, plasma triglycerides and antioxidative vitamins may partly account for the increased LDL oxidation susceptibility found in Vilnius men compared with Link?ping men.     

Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats

There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.     

Hypertriglyceridemia in pregnancy does not contribute to the enhanced formation of remnant lipoprotein particles

BACKGROUND: During pregnancy, serum cholesterol (TC) and triglyceride (TG) concentrations are known to increase significantly, but whether remnant lipoprotein particles (RLP) increase has not been shown. METHODS: We compared lipid profiles in 22 healthy pregnant women to 31 healthy nonpregnant women and 24 patients with diabetes mellitus (DM), by measuring cholesterol and TG concentrations in major lipoprotein classes after HPLC separation and immunoseparation of RLP. RESULTS: Serum TG and TC concentrations were significantly higher in the pregnant group than in the healthy control or DM groups. Cholesterol and TG concentrations of all major lipoprotein classes were also significantly higher in the pregnant group than the control and DM groups, except for VLDL-TG in the DM group. RLP-C and RLP-TG concentrations were significantly higher in the pregnant group (8.7 mg/dl and 25.4 mg/dl on average) than the control group (2.4 mg/dl and 5.7 mg/dl), but not different from the DM group (8.8 mg/dl and 24.1 mg/dl). RLP-TG to RLP-C ratios were similar among the three groups and correlated with the VLDL-TG to VLDL-C ratio. The percentages of RLP-C in VLDL-C and RLP-TG in VLDL-TG in the pregnant group (15.9% and 15.7%) were significantly lower than those of the control (48.5% and 35.6%) and the DM (32.7% and 20.8%) groups. CONCLUSIONS: RLP increased moderately during gestation with the increase in VLDL and TG, but the percentage of RLP in VLDL was significantly lower in the pregnant women compared with the control and DM patients, suggesting that hypertriglyceridemia in pregnancy is not primarily due to an increase in the atherogenic RLP.     

Endothelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease.

The oxidative modification of low-density lipoprotein (LDL) may be dependent or independent of lipid peroxidation. This peroxidation may be initiated by metal ions, possibly in association with phospholipase activity or catalyzed by myeloperoxidase independent of metal ions. It results in the generation of aldehydes, which substitute lysine residues in the apolipoprotein B-100 moiety and thus in the generation of oxidized LDL. Endothelial injury, associated with increased production of free radicals during oxidative stress, is associated with increased prostaglandin synthesis and platelet adhesion/activation. These processes are associated with the release of aldehydes, which induce the oxidative modification of LDL in the absence of lipid peroxidation and thus in the generation of malondialdehyde (MDA)-modified LDL. We have demonstrated an association between coronary artery disease (CAD) and increased plasma levels of oxidized LDL. The increase of circulating oxidized LDL is most probably independent of plaque instability. Indeed, plasma levels of oxidized LDL were very similar for patients with stable CAD and for patients with acute coronary syndromes. Acute coronary syndromes, however, were associated with increased release of MDA-modified LDL that was independent of the necrosis of myocardial cells. These data suggest that oxidized LDL is a marker of coronary atherosclerosis whereas MDA-modified LDL is a marker of plaque instability. Recently, a prospective study in cardiac transplant patients suggested an active role of oxidized LDL in the development of CAD. Oxidized LDL may contribute to the progression of atherosclerosis by enhancing endothelial injury by inducing foam cell generation and smooth muscle proliferation.     

血清三酰甘油水平与小而密低密度脂蛋白胆固醇的关系

目的探讨健康人群和血脂代谢异常者小而密低密度脂蛋白胆固醇（sdLDL-C）水平分布及血清三酰甘油（TG）水平对sdLDL-C水平的影响。方法将693例血脂代谢异常者分为A组（542例,TG〈1.70 mmol/L）和B组（151例,TG≥1.70 mmol/L）,同时选取健康对照者181名。采用肝素-镁沉淀法检测血清sdLDL-C水平,同时检测空腹血糖、血脂[包括总胆固醇（TC）、TG、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]及载脂蛋白A1（apo A1）、载脂蛋白B（apo B）。分析各组各指标间的差异及血清TG水平对sdLDL-C的影响。结果 B组TC、aopB水平高于健康对照组和A组（P〈0.05）,HDL-C水平明显低于健康对照组和A组（P〈0.05）。健康对照组sdLDL-C水平呈偏态分布,以第95百分位数（0.62 mmol/L）作为正常参考阈值。血脂异常组sdLDL-C水平为0.46（0.34～0.64）mmol/L,明显高于健康对照组[0.22（0.16～0.38）mmol/L]（P〈0.001）。多元逐步回归分析表明,对sdLDL-C水平有显著影响的因素为TG和LDL-C。17.6%的A组患者血清sdLDL-C水平高于正常参考阈值（P〈0.05）。受试者工作特征（ROC）曲线分析表明,TG识别sdLDL-C水平升高的Cut-off值为1.36 mmol/L。结论血清sdLDL-C水平受TG的影响最大,判断sdLDL-C水平是否升高的TG的界值应适当调低。     

Decreased large artery distensibility in borderline hypertension is related to increased in vivo low-density lipoprotein oxidation

The present study tested the hypothesis that reduced arterial elasticity seen in hypertension is related to increased oxidation of LDL. Fifteen men with borderline hypertension (BHT), with blood pressure values classified as high normal (systolic blood pressure 130-140 mmHg or diastolic blood pressure 85-89 mmHg) were included. The control group comprised 22 men with normal blood pressure values (<135/80 mmHg) matched for age, body size and LDL-cholesterol level. Distensibility of aorta was measured using magnetic resonance imaging, and distensibility of the common carotid artery using ultrasound. Baseline LDL diene conjugation was used as a marker for ox-LDL. Aortic and carotid distensibilities were lower in the BHT men than in controls (1.4 +/- 0.6 vs. 1.9 +/- 0.6%/10 mmHg, p<0.05 for aortic distensibility; 2.9 +/- 0.9 vs. 3.6 +/- 0.6%/10 mmHg, p<0.05 for carotid distensibility). Ox-LDL was significantly higher in the BHT men than in controls (44 +/-15 vs. 28 +/- 8 micromol/L, p<0.01). In univariate analysis, ox-LDL associated with aortic distensibility (r=-0.43, p<0.05). In multivariate analysis, the differences in distensibilities between the groups disappeared when the values were adjusted for ox-LDL. These data show decreased arterial elasticity and increased LDL oxidation in young men with borderline hypertension, and suggest that oxidative modification of LDL particles may play a pathophysiological role in the development of reduced arterial distensibility in hypertension.     

Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.

BACKGROUND: Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. METHODS: In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose atorvastatin (80 mg) and conventional-dose simvastatin (40 mg) on LDL subfraction profile (n = 289), LDL oxidizability (n = 121), and circulating autoantibodies to oxidized LDL (n = 220). Progression of atherosclerosis was measured by carotid intima media thickness (IMT) (n = 325). RESULTS: At baseline, the patients showed an intermediate LDL subfraction profile composed of three LDL subfractions (LDL1, LDL2, LDL3), with LDL2 as the predominant subfraction. A strong negative correlation was found between plasma triglycerides and the LDL subfraction profile (r = -.64, p = .000). Both plasma levels of triglycerides and small dense LDL3 correlated weakly with baseline IMT (r = .11, p = .04 and r = .15, p = .01, respectively; n = 289). No association was found between baseline IMT and oxidation parameters or circulating antibodies to oxidized LDL. Atorvastatin reduced triglycerides, LDL cholesterol, and all LDL subfractions to a greater extent than did simvastatin and led to regression of carotid IMT. However, LDL subfraction pattern and plasma levels of autoantibodies to oxidized LDL remained unchanged in both treatment groups, and LDL oxidizability increased minimally to a similar extent in both groups. Significant treatment differences were found for the rate of in vitro oxidation of LDL and the amount of dienes formed during in vitro oxidation of LDL, which both decreased more following atorvastatin than after simvastatin. CONCLUSION: Change of IMT after statin treatment was associated with baseline IMT (r = .41), LDL cholesterol (r = -.20), and the amount of dienes formed during in vitro oxidation of LOL (r = .28) but not with plasma levels of antibodies to oxidized LDL, in vitro LDL oxidizability, and LDL subfraction profile.     

Lovastatin enhances paraoxonase enzyme activity and quells low-density lipoprotein susceptibility to oxidation in type 2 diabetic nephropathy

Objectives:To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN).Design and methods:Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes.Results:After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and < 0.001), while after 30 days of lovastatin withdrawal, PON1 and ARE activities and LDL-C lag phase had not changed significantly.Conclusion:Lovastatin therapy improves PON1 and ARE activities, and LDL-C susceptibility to oxidation. Despite withdrawal of lovastatin, PON1 and ARE activities, and LDL-C susceptibility to oxidation remain unchanged in people with T2DN.     

Correlation between the ratio of serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with that of serum apolipoproteins B and A-I

Summary Phosphowolframate/magnesium chloride, a commonly used precipitation method for the determination of high-density lipoprotein cholesterol in human serum, yields a supernatant containing almost all of the lipoproteins apo A-I and apo A-II but no lipoprotein apo B. The correlation between high-density lipoprotein cholesterol and apo A-I was very high (r=0.94), as well as that between the precipitation method and ultracentrifugal analysis (r>0.95,P<0.001). In contrast, detergent precipitation (for the determination of low-density lipoprotein cholesterol in human serum) produced sediments which contained the major proportion of apo B and only minor amounts of apo A-I and apo A-II. The precipitation method for low-density lipoprotein cholesterol showed very good agreement with ultracentrifugal analysis (r=0.99). Yields of 80.2% were obtained for apo B with both methods. Results obtained using the precipitation methods showed excellent agreement with those obtained using the Friedewald formula (r>0.99). Results were also very similar when hypertriglyceridemic serum samples were briefly centrifuged before analysis of cholesterol, high-density lipoprotein cholesterol and triglyceride values. The present study shows highly significant correlations between cholesterol/high-density lipoprotein cholesterol or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apo B/apo A-I ratios (P<0.001). Apo B and apo A-I levels could be used in addition to low- and high-density lipoprotein cholesterol values when assessing the risk of cardiovascular disease, if the methods for determining serum apolipoproteins have been properly standardized.     

Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density lipoprotein oxidation

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects. METHODS: Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO(3)(-)) determination and plasma oxidized LDL was determined by a capture ELISA. RESULTS: Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels. CONCLUSIONS: There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.     

Phosphoethanolamine-complexed C-reactive protein: a pharmacological-like macromolecule that binds to native low-density lipoprotein in human serum

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defence against oxidizing agents and in reductive biosynthetic reactions. Many variants of G6PD have been described, mostly produced from missense mutations, with wide ranging levels of enzyme activity and associated clinical symptoms. METHOD: A single base extension assay is used, yielding a single base difference of the extended products. Primers are designed to amplify products of different sizes with distinct fluorescent dyes in order to accurately distinguish all possible combinations of genotypes (homozygous and heterozygous for each mutation) in a multiplex PCR analysis. RESULTS: We present the first application of a multiplex multicolour assay to detect 15 of the most frequent G6PD-related mutations in Spain, which are studied in three multiplex reactions. Capillary electrophoresis analysis of the amplified products enables easy, rapid, unambiguous and high-resolution discrimination between wild-type and mutant alleles, even though various mutations may be present in the multiplex analysis. CONCLUSION: The analytical method described herein offers greater diagnostic power in Spanish and Mediterranean populations and would facilitate automated genotyping in routine molecular diagnostics and large-scale genetic studies (e.g., newborn screening programs).     

Effect of hormone replacement therapy on the susceptibility of low-density lipoprotein to oxidation among postmenopausal hypercholesterolaemic women

The effect of sequential combined hormone replacement therapy on the susceptibility of low-density lipoprotein to oxidative modification was investigated in a double-blind, randomized placebo-controlled study. Hypercholesterolaemic, postmenopausal women were supplemented with 17β-oestradiol and norethisterone acetate ( n =13 subjects) or placebo capsules ( n =15 subjects) for 12 weeks. They were instructed to follow the American Heart Association step one diet. Low-density lipoprotein, isolated before and after treatment, was subjected to copper-catalysed lipid peroxidation. There were no significant differences between low-density lipoprotein from the hormone replacement therapy and placebo groups, as assessed by measuring the lag time for formation of conjugated dienes, the rate of formation and the amount of conjugated dienes formed, the amount of lipid peroxides generated, and the relative electrophoretic mobility at baseline and after treatment. Dietary records showed that the subjects were consuming similar amounts of fat and vitamins. No major differences were found in the fatty acid pattern of low-density lipoprotein from the two groups. In conclusion, the results indicated that hormone replacement therapy with 17β-oestradiol sequentially combined with norethisterone acetate in non-smoking, hypercholesterolaemic, postmenopausal women has no protective effect on the susceptibility of low-density lipoprotein to copper-catalysed modification in vitro .     

急性、非急性冠状动脉病变患者血浆氧化低密度脂蛋白的变化

目的探讨冠心病患者氧化型低密度脂蛋白(ox-LDL)的变化及机制,评估ox-LDL水平检测的临床价值。方法采用ELISA法测定139例冠心病组患者[急性冠状动脉综合征(ACS)76例,非ACS组63例]和100例健康对照组人群血浆ox-LDL水平;根据冠状动脉造影结果将冠心病组分为多支病变组、双支病变组和单支病变组进行比较分析。结果ACS组患者和非ACS组患者ox-LDL水平均显著高于健康对照组[ACS:(188.01±69.88)μg/ml,非ACS:(137.88±59.74)μg/ml,对照组:(82.68±29.06)μg/ml;P均<0.001];且ACS组患者ox-LDL水平显著高于非ACS组患者(P<0.001)。冠状动脉多支、双支、单支病变组间ox-LDL水平不同[(183.63±79.42)μg/ml,(164.15±63.79)μg/ml和(146.97±58.40)μg/ml,P<0.05],多支高于单支(P<0.01)。多因素分析显示冠状动脉病变程度仅与ox-LDL相关(R2=0.048,β=0.217,P=0.000)。结论冠心病患者ox-LDL水平升高,与病变程度相关,急性冠脉综合...     

Role of ascorbic acid on in vitro oxidation of low-density lipoprotein derived from hypercholesterolemic patients

BACKGROUND: The susceptibility of low-density lipoprotein (LDL) to oxidation is thought to be a crucial factor responsible for atherogenesis. There is substantial evidence for a role of dietary antioxidants in the prevention of atherogenesis and the protective effect of antioxidant nutrients may be mediated through inhibition of the oxidative modification of LDL. METHODS: We performed in vitro oxidation of LDL derived from normal and hypercholesterolemic individuals in absence and presence of different doses of ascorbic acid. RESULTS: The serum lipid peroxidation level was significantly increased in hypercholesterolemic patients and their LDL has shown a greater propensity towards in vitro oxidation. Hypercholesterolemic LDL required a higher amount of ascorbic acid to reduce its oxidation level as compared to LDL isolated from normocholesterolemic individuals. CONCLUSION: This observation may be of importance in designing future studies of antioxidant supplementation in patients with hypercholesterolemia which is one of the major risk factors for atherosclerosis.