Positive correlation between in vivo oxidized LDL and LDL immune complexes

OBJECTIVES: To investigate the possible relationship between oxidized low-density lipoprotein (ox-LDL) and LDL immune complexes (IC). METHODS: Both LDL-IC and ox-LDL were detected by sandwich ELISA. The levels were also studied in 60 patients with coronary heart disease (CHD) and 50 control subjects. RESULTS: Compared to controls, both the plasma ox-LDL concentrations (595.5 +/- 194.8 vs. 440.3 +/- 175.0 microg/l, P < 0.001) and LDL-IC levels (2.74 +/- 0.73 vs. 1.38 +/- 0.78 AU, P < 0.001) in the patients with CHD were significantly increased. The relationships between LDL-IC, ox-LDL levels, and other lipid parameters in all the studied subjects (n = 100) were analyzed. LDL-IC levels were positively correlated with TC, TG, LDL-C, lipoprotein(a) [Lp(a)], and apolipoprotein B (apoB) concentration, while negatively correlated with apoA1 concentration, respectively. Similarly, ox-LDL levels were also found positively correlated with TC, LDL-C, and apoB concentrations, respectively. Furthermore, a significantly positive correlation between ox-LDL and LDL-IC levels was found (r = 0.313, P < 0.005). CONCLUSION: In vivo oxidized LDL positively correlates with circulating levels of LDL immune complexes.     

High oxidized LDL and elevated plasma homocysteine contribute to the early reduction of myocardial flow reserve in healthy adults

BACKGROUND: Impairment of coronary blood flow reserve has been shown to be an early manifestation of atherosclerosis and coronary artery disease (CAD). We studied more closely the contribution of various risk factors on early deterioration of coronary function. MATERIALS AND METHODS: Fifty-one young, apparently healthy adults, with normal or mildly elevated serum cholesterol levels but without other major risk factors for CAD, such as diabetes or hypertension, underwent positron emission tomography (PET) studies. Coronary flow reserve (CFR) was measured using O15-water. In addition to the classical risk factors, the role of several new risk indicators, such as low-density lipoprotein (LDL) oxidation, infection (Chlamydia pneumoniae antibodies), and inflammation parameters (adhesion molecules, ICAM, VCAM, selectin, and C-reactive protein), homocysteine and body iron stores were investigated. RESULTS: Elevated lipid and lipoprotein levels were not associated with reduced coronary reactivity. However, high autoantibody titers against oxidized LDL (oxLDL) were associated with 21% lower CFR than low oxLDL (P < 0.05). Furthermore, high homocysteine levels predicted low CFR (P < 0.05). The other measured parameters, Chlamydia pneumoniae antibody levels, C-reactive protein and adhesion molecule concentrations did not associate with myocardial blood flow. In a stepwise regression model, oxLDL (P = 0.03), homocysteine (P = 0.04) and triglycerides (P = 0.018) were significant predictors of CFR. CONCLUSIONS: The present study suggests an important role for oxidized LDL and plasma homocysteine on early impairment of coronary reactivity in young adults.     

Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease

BACKGROUND: Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD). MATERIALS AND METHODS: Eighty men and 27 women with clinically suspected CAD underwent quantitative coronary angiography (QCA). TRLs were isolated by density gradient ultracentrifugation before and 6 h after an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by ELISA, and LDL size by gradient gel electrophoresis. RESULTS: Triglycerides, apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units (Sf) > 400 and in Sf 12-400 fractions were markedly increased at 6 h. Postprandial cholesterol content of RLPs (RLP-C) correlated with respective triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf > 400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r = -0.459 and r = -0.442, respectively). (P < 0.001 for all). OxLDL was elevated postprandially (P < 0.001). In multivariate analysis, oxLDL was a determinant of severity and extent of CAD. CONCLUSION: Postprandial state is associated with oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and is associated with coronary atherosclerosis.     

Correlation between plasma total homocysteine and copper in patients with peripheral vascular disease

BACKGROUND: Increased concentrations of both plasma total homocysteine and copper are separately associated with cardiovascular disease. Correlations between plasma total homocysteine, trace elements, and vitamins in patients with peripheral vascular disease have not been investigated. METHODS: The concentrations of trace elements in plasma were determined by the multielement analytical technique of total-reflection x-ray fluorescence spectrometry. Plasma total homocysteine was determined by HPLC. RESULTS: In the univariate and multivariate regression analyses, copper was positively correlated with plasma total homocysteine in all subjects (coefficient +/- SE, 0.347 +/- 0.113; P = 0.0026 and coefficient +/- SE, 0.422 +/- 0.108; P = 0.0002, respectively), and in patients with peripheral vascular disease (coefficient +/- SE, 0.370 +/- 0.150; P = 0.016; and coefficient +/- SE, 0.490 +/- 0.151; P = 0.0025, respectively). Correlation between copper and plasma total homocysteine was not detected in healthy control subjects. The concentration of calcium in plasma (67.5 vs 80. 8 microg/g) was significantly lower in the patients than in the control subjects (P = 0.02). When the patients were divided into groups, the patients with suprainguinal lesions had significantly higher copper concentrations (P = 0.04) and significantly lower selenium and calcium concentrations (P = 0.01 and 0.008, respectively) than the healthy subjects. Patients had higher concentrations of autoantibodies against oxidized LDL and concentrations of thiobarbituric acid-reactive substance than the healthy subjects (P <0.0001 and P = 0.001, respectively). The concentrations of plasma total homocysteine and alpha-tocopherol were significantly higher, and the concentrations of vitamin B(6) and beta-carotene were lower in the patients than the healthy subjects. CONCLUSION: Our findings suggest that the atherogenicity of homocysteine may be related to copper-dependent interactions.     

Antibodies to oxidized LDL in atherosclerosis development--clinical and animal studies

Atherosclerotic lesions represent the principal cause of death in western industrialized countries. Immune mechanisms have been suggested to play a key role in the development of atherosclerosis. Several lines of evidence support that oxidized LDL (oxLDL) may be a key antigen in atherosclerosis. Antibodies to oxLDL have been found in human and rabbit plasma and in atherosclerotic lesions. So far, it has not been well established if the immune response is predominantly pro- or antiatherogenic. During the last decade, numerous studies have been performed investigating the relationship between circulating antibodies in plasma in relation to endothelial dysfunction, subclinical atherosclerosis and cardiovascular events in different patient categories. Taken together, these studies have shown diverging results. However, most studies have shown that elevated IgG titers to oxLDL are related to atherosclerotic disease. Even if fewer studies have investigated IgM titers, most studies seem to show an inverse relationship between IgM titers and atherosclerotic disease. In animal studies, it has been shown that immunization with oxLDL induces antibody formation (both IgG and IgM) and protects against atherosclerosis development. Furthermore, it has also been shown that immunization with Streptococcus pneumoniae induce an IgM response, which is associated with decreased atherosclerosis development, and plasma from these mice also has the ability to block uptake of oxLDL to macrophages. To conclude, antibodies to oxLDL in clinical cardiovascular disease show diverging results, while animal studies suggest that immunization may have a beneficial role in atherosclerosis development. Prospective and intervention studies, as well as mechanistic studies are clearly needed to elucidate the possible causal role of antibodies to oxLDL in man.     

Minimally modified electronegative LDL and its autoantibodies in acute and chronic coronary syndromes

OBJECTIVES: To determine the minimally modified electronegative LDL (LDL-) and its autoantibodies in coronary syndromes. DESIGN AND METHODS: LDL(-) and its autoantibodies were determined by ELISA in patients with acute (ACS, unstable angina; AMI, acute myocardial infarction) and chronic coronary syndromes (stable angina, SA) and compared to subjects without coronary disease (controls). Results are expressed as median of LDL- (microg/mL) and anti-LDL(-) IgG (OD405 nm). RESULTS: The concentrations of LDL(-) were higher in patients with coronary disease (ACS: 40.7 microg/mL; SA: 35.0 microg/mL) as compared to controls (21.6 microg/mL). The highest LDL- concentrations were found in patients with AMI (41.8 microg/mL). Anti-LDL(-) IgG was elevated in ACS (1.143) in relation to CCS (0.527) and controls (0.467). A positive correlation was observed between anti-LDL- IgG and CRP levels (r = 0.34, p <0.01) in the studied groups. CONCLUSIONS: LDL(-) and anti-LDL(-) autoantibodies may be useful markers to follow patients with high risk for coronary events.     

Oxidation of LDL enhances the cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester transfer rate to HDL, bringing on a diminished net transfer of cholesteryl ester from HDL to oxidized LDL

Cholesteryl ester transfer protein (CETP) plays a controversial role in atherogenesis by contributing to the net transfer of high density lipoprotein (HDL) cholesteryl ester (CE) to the liver via apolipoprotein-B-containing lipoproteins (apoB-LP). We evaluated in vitro the CETP-mediated bidirectional transfer of CE from HDL to the chemically modified pro-atherogenic low density lipoprotein (LDL) particles. Acetylated or oxidized (ox) LDL, either unlabeled or [3H]-CE labeled, were incubated with [14C]-CE-HDL in the presence of the lipoprotein-deficient plasma fraction (d>1.21 g/ml) as the source of CETP. The amount of radioactive CE transferred was determined after dextran sulfate/MgCl(2) precipitation of LDL. The results showed a 1.4-2.8-fold lower HDL-CE transfer to acetylated LDL while no effect was observed on the CE transfer to oxidized LDL. However, the reverse transfer rate of [3H]CE-LDL to HDL was 1.4-3.6 times greater when LDL was oxidized than when it was intact. Overall, HDL(2) was better than HDL(3) as donor of CE to native LDL, probably reflecting the relatively greater CE content of HDL(2). Oxidation of LDL enhanced the CETP-mediated cholesteryl ester transfer rate to HDL, bringing on a reduced net transfer rate of cholesteryl ester from HDL to ox LDL. This may diminish the oxLDL particle's atherogenic effect.     

Increased serum sialic acid levels in primary osteoarthritis and inactive rheumatoid arthritis

Accumulation of oxidized proteins and impaired antioxidant system have been shown to be associated with arthritis. Serum sialic acid (SA) is known as a parameter of inflammation. In the present study, to explore the potential role of SA in arthritis, we measured serum SA levels, plasma protein oxidation, and antioxidant status in patients with primary osteoarthritis (POA) and inactive rheumatoid arthritis (RA). Inactive RA (iRA) was defined upon the American College of Rheumatology criteria for clinical remission of RA. A total of 40 patients (20 POA patients, including 4 male subjects, and 20 iRA female patients) and 20 healthy female subjects were included in this study. SA, antioxidants, and protein oxidation levels were determined spectrophotometrically in serum or plasma samples. Serum SA levels were significantly increased in POA (3.34 +/- 0.37 mM, p < 0.0001) and iRA (3.11 +/- 0.47 mM, p < 0.05), compared with healthy controls (2.41 +/- 0.16 mM). Plasma total antioxidant activity, plasma superoxide dismutase activity and serum reduced glutathione levels were significantly decreased in patients with POA and those with iRA, whereas plasma carbonyl content and serum total protein were increased in those patients. Moreover, plasma total thiol levels were significantly increased in iRA and decreased in POA. Thus, increased SA and protein oxidation levels are associated with the decreased antioxidant levels in POA and iRA patients. These results suggest that SA may be considered as a potent defense molecule against oxidative damage in arthritis. Antioxidant therapy may halt or ameliorate the progression of arthritis.     

High plasma levels of CD40 are associated with low coenzyme Q and vitamin E content of low-density lipoprotein in healthy men

OBJECTIVE: There is a growing body of evidence to suggest that low-density lipoprotein (LDL) cholesterol, inflammation and oxidative stress are pivotal in the development of cardiovascular disease, but their interconnections are not well known. The objective of this study was to determine whether immunological activation, reflected by the plasma levels of soluble CD40 (sCD40), interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6 are associated with the antioxidant potential of LDL particles or with common lipid, immunological or thrombotic markers in 51 young healthy men. MATERIAL AND METHODS: We determined the coenzyme Q level from an oxidized LDL fraction, obtaining the concentration for ubiquinone, which indicates total coenzyme Q levels. RESULTS: The plasma level of sCD40 was negatively correlated with LDL ubiquinone (r=-0.45, p=0.001) and E vitamin (r=-0.37, p=0.008) and positively correlated with plasma concentration of plasminogen activator inhibitor-1 (PAI-1, r=0.52, p=0.002) and caspase-1 (r=0.40, p=0.004). No correlation was detected between sCD40 and plasma lipid or C-reactive protein concentrations. As sCD40 was strongly correlated with the content of LDL ubiquinone and vitamin E, their values were compared according to groups formed by sCD40 tertiles. Analysis of variance showed that there were significant differences in LDL ubiquinone (p<0.0001) and vitamin E (p=0.004) concentrations between sCD40 tertiles. CONCLUSIONS: The data indicate that increased activation of the CD40 system is related to low levels of LDL ubiquinone and vitamin E. This suggests that chronic or increased immunological activation may consume the antioxidant potential of LDL particles.     

Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer

OBJECTIVES: The aim of this study was to evaluate the extent of oxidative stress in patients with breast or ovarian cancer by analyzing the magnitude of serum oxidizability and the involvement of oxidized low-density lipoproteins (oxLDL) in the disease. DESIGN AND METHODS: The study was conducted on 32 patients diagnosed with breast or ovarian cancer but who had not undergone any kind of treatment and 30 healthy individuals of similar age. The evaluation of oxidative stress was assessed by: (a) the ex-vivo susceptibility of serum lipids to oxidation and (b) the detection of oxLDL and anti-oxLDL autoantibodies. Total cholesterol, LDL-cholesterol and HDL-cholesterol were co-estimated. RESULTS: The results indicated that the levels of oxLDL were increased among both breast and ovarian cancer patients as compared to the control subjects. Additionally in patients with breast cancer, serum total cholesterol, LDL-cholesterol, anti-oxLDL antibodies and the maximal rate of diene formation (RA), the index of oxidizable components load, were increased in comparison to controls. There is statistically significant evidence that serum oxLDL levels are associated with increased risk of breast and ovarian cancer. CONCLUSIONS: The findings exhibit a correlation between oxLDL and malignancy, supporting the contribution of oxidative stress to carcinogenesis and the possible involvement of oxLDL in the process of malignancy. The clinical evaluation of the oxLDL measurement is under investigation.     

PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1

In addition to its role in energy storage, adipose tissue also accumulates cholesterol. Concentrations of cholesterol and triglycerides are strongly correlated in the adipocyte, but little is known about mechanisms regulating cholesterol metabolism in fat cells. Here we report that antidiabetic thiazolidinediones (TZDs) and other ligands for the nuclear receptor PPARgamma dramatically upregulate oxidized LDL receptor 1 (OLR1) in adipocytes by facilitating the exchange of coactivators for corepressors on the OLR1 gene in cultured mouse adipocytes. TZDs markedly stimulate the uptake of oxidized LDL (oxLDL) into adipocytes, and this requires OLR1. Increased OLR1 expression, resulting either from TZD treatment or adenoviral gene delivery, significantly augments adipocyte cholesterol content and enhances fatty acid uptake. OLR1 expression in white adipose tissue is increased in obesity and is further induced by PPARgamma ligand treatment in vivo. Serum oxLDL levels are decreased in both lean and obese diabetic animals treated with TZDs. These data identify OLR1 as a novel PPARgamma target gene in adipocytes. While the physiological role of adipose tissue in cholesterol and oxLDL metabolism remains to be established, the induction of OLR1 is a potential means by which PPARgamma ligands regulate lipid metabolism and insulin sensitivity in adipocytes.     

Sialic acid content of LDL and lipoprotein metabolism in combined hyperlipidemia and primary moderate hypercholesterolemia.

Low density lipoprotein (LDL) with low sialic acid content has been shown to cause intracellular lipid accumulation and therefore is suggested to be atherogenic. We investigated the sialic acid content of total LDL and its subfractions, and their relations to lipoprotein kinetics in 22 subjects with primary moderate hypercholesterolemia (IIa) and in 21 subjects with combined hyperlipidemia (IIb) matched for age, sex, BMI and the frequency of coronary artery disease. Sialic acid to protein ratio decreased gradually from VLDL and IDL to light and dense LDL and HDL, but was high in very dense LDL probably due to presence of Lp(a). Sialic acid to apo B ratio was significantly lower in dense and very dense subfractions of IIb than IIa. The sialic acid/apo B ratios of dense and very dense LDL subfractions were interrelated and were negatively associated with their cholesterol and triglyceride concentrations, and with the transport rate (TR) for dense LDL apo B. The only metabolic variable differing between the groups was the TR for dense LDL apo B, which was significantly higher in IIb vs. IIa. In addition, the TR for dense LDL apo B was positively associated with the esterification percentage of LDL cholesterol. In conclusion, low sialic acid content in dense and very dense LDL subfractions was associated with enhanced TR for LDL apo B and type IIb dyslipidemia.     

糖尿病患者血浆氧化、丙二醛修饰低密度脂蛋白及其自身抗体水平

目的探讨血浆氧化及丙二醛（MDA）修饰低密度脂蛋白（LDL）及其自身抗体与糖尿病（DM）及其他血脂项目之间的关系。方法选择DM患者、正常对照组各60例。采用酶联免疫吸附试验（ELISA）分别测定铜离子氧化型LDL（ox-LDL）、MDA修饰型LDL（MDA-LDL）及其自身抗体,同时对受检者血脂水平进行检测。结果DM患者血浆ox-LDL、MDA-LDL及其自身抗体水平均明显高于对照组（P〈0．01）,分别与总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）呈高度正相关,而与高密度脂蛋白胆固醇（HDL-C）呈负相关;且ox-LDL、MDA-LDL分别同其自身抗体呈高度正相关。结论DM患者ox-LDL、MDA-LDL及其自身抗体水平显著升高,可能参与动脉粥样硬化的发生、发展过程。     

Factors affecting S-homocysteinylation of LDL apoprotein B

BACKGROUND: Hyperhomocysteinemia is an important risk factor for vascular disease and atherosclerosis, but the mechanisms by which homocysteine exerts its deleterious effects are not known. Because oxidation and/or homocysteinylation may increase atherogenicity of LDL, we investigated S-homocysteinylation of LDL as a possible contributor to atherosclerosis pathogenesis. METHODS: We used capillary electrophoresis to measure LDL-bound thiols [homocysteine, cysteine (Cys), cysteinylglycine, glutathione, and glutamylcysteine] in 104 healthy study participants We also assessed total plasma thiol concentrations and lipid profiles. RESULTS: Our data suggest that apoprotein B (apoB)-cysteinylglycine (CysGly), apoB-Hcy, and apoB-Cys concentrations are markedly higher in men than in women. The percentage of CysGly and glutathione on apoB was higher than that of the same thiols in plasma, whereas the other thiols were markedly less prevalent in lipoprotein than in plasma. Pearson correlation showed that among all thiols, only total plasma Hcy is related to apoB-Hcy concentrations. Multiple correlation analysis confirmed that total Hcy was the most important determinant of apoB-Hcy. Age and LDL cholesterol also showed positive associations, but Cys and, mainly, CysGly were negatively associated with apoB-Hcy concentrations. CONCLUSIONS: apoB-Hcy derivative formation is mainly dependent on total homocysteine concentration. Increased cholesterol concentrations are related to increased apoB-Hcy. CysGly seems to compete with Hcy for binding to LDL apoprotein, suggesting that CysGly may protect against atherosclerosis by decreasing the concentrations of Hcy transferred by LDL from plasma to endothelial and subendothelial spaces.     

人血清氧化低密度脂蛋白自身抗体的提取和初步鉴定

目的提取和鉴定人血清氧化低密度脂蛋白(Ox-LDL)自身抗体.方法采用溴化氰活化的Sepharose 4B交联Ox-LDL制备免疫吸附层析柱,从正常人血清中提取抗Ox-LDL自身抗体,采用ELISA法鉴定其免疫反应性,散射免疫比浊法分析自身抗体种类.结果用NaHCO3、醋酸盐和KCNS溶液洗脱,分别收集洗脱峰.8份正常人血清中均收集到Ox-LDL自身抗体,与Ox-LDL均具有良好的反应性.自身抗体种类中以IgG为主,其次为IgM.结论此法提取的抗Ox-LDL自身抗体同Ox-LDL具有良好的反应能力.     

Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL

BACKGROUND: Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to be susceptible to oxidation. METHODS: We measured LDL particle size, using gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using an ELISA, and investigated the association between triglyceride (TG) concentrations, LDL size, and MDA-LDL. RESULTS: TG concentrations correlated negatively with the predominant LDL size (r = -0.650) and HDL-C concentration (r = -0.556). The relationship between TG concentration and LDL size, evaluated by measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG concentrations and four distribution ranges of LDL size. These experiments indicated that there is a threshold for oxidation susceptibility at an LDL size of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C, apolipoprotein B, and total cholesterol), we evaluated them in control subjects and patients with diabetes mellitus or hypertriglyceridemia. When the size range for normal LDL was postulated to be 25.5 < or = phi (LDL diameter) < 26.5 nm, the MDA-LDL concentration was significantly higher in the subgroups of patients with LDL in the size range 24.5 < or = phi < 25.5 nm compared with patients with normal LDL. This result also suggests that the threshold is at a LDL size of 25.5 nm. CONCLUSION: The threshold for oxidation susceptibility coincided with the point of LDL size separation between the LDL subclass patterns A and B as an atherosclerotic risk.     

Increase in plasma total and lipoprotein cholesterol during incubation of whole blood samples at 37 degrees C--influence of LCAT inhibitors.

Incubation of whole blood samples at 37 degrees C caused a time-dependent increase in plasma cholesterol concentrations. In samples from 40 fasting healthy males, plasma cholesterol rose by 13.6 +/- 3% during 24 h (P less than 0.001). Changes in cholesterol concentrations were found in both the HDL fraction and the VLDL/LDL fraction. The increase in lipoprotein cholesterol concentrations correlated positively with the initial levels of HDL cholesterol and apo A-I; and with the original levels of VLDL/LDL cholesterol, apo B and triglycerides. The increase in plasma total cholesterol was not related to the HDL cholesterol and apo A-I concentrations. It was more pronounced in samples with elevated plasma concentrations of total cholesterol, VLDL/LDL cholesterol, apo B and triglycerides. The elevation in plasma total cholesterol resulted from an increase in cholesteryl esters, whereas free cholesterol decreased. After LCAT inhibition no changes in total, free and esterified cholesterol were observed. Therefore, increase in plasma cholesterol seems to represent a LCAT-dependent cholesterol transport out of blood cells.     

Oxidized LDL, anti-oxidized LDL and anti-annexin A5 antibodies in primary antiphospholipid syndrome

The aim of this study was to compare whether oxidized LDL (oxLDL), anti-oxLDL and anti-annexin (anx) A5 antibodies are associated with clinical features of primary antiphospholipid syndrome (PAPS), and to compare these to well-defined groups of non-PAPS myocardial infarction survivors (non-PAPS MI) and to non-PAPS patients with pulmonary emboli (non-PAPS PE). All parameters investigated were analyzed by ELISA using commercial reagents. PAPS patients with MI, in comparison to the group of non-PAPS MI survivors, had significantly elevated concentrations of oxLDL (p = 0.003) and anti-oxLDL antibodies (p = 0.024). Anti-anxA5 antibodies of the IgG isotype were associated with recurrent abortions (OR = 4.788, p = 0.036, 95% CI: 1.104 - 20.762). OxLDL and anti-oxLDL antibodies represent additional risk factors which, together with other factors, might lead to complications of arterial thromboses, such as myocardial infarctions in PAPS, while association of IgG anti-anxA5 antibodies with recurrent abortions is a reflection of the small number of patients with this feature involved in the study and should therefore be investigated further.     

Oxidized low-density lipoprotein autoantibodies in patients with primary gout: effect of urate-lowering therapy

BACKGROUND: Uric acid is a strong scavenger of reactive oxygen species, which are known to contribute to the development of atherosclerosis, while the incidence of atherosclerotic diseases is rather high in patients with gout. Among the established risk factors for atherosclerosis, oxidized LDL is believed to play a major role in its development and progression. Allopurinol and its active metabolite, oxypurinol, have been suggested to possess an antioxidant ability to scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The objective of this work was to determine the degree of LDL oxidation in gout and the effect of allopurinol on LDL oxidation. METHODS: Age-matched male patients with primary intercritical gout and healthy male adults were included in the study. The serum concentrations of oxidized LDL autoantibodies and total antioxidant status were measured using an enzyme immunoassay. RESULTS: Serum concentrations of oxidized LDL autoantibodies were significantly higher in patients with gout than the control subjects (p < 0.05) and were significantly decreased after allopurinol treatment (p < 0.05), but not by benzbromarone treatment, in spite of the similar concentrations of uric acid and total antioxidant status in serum following their separate administration. CONCLUSIONS: Although the exact mechanism remains unclear, increased serum concentrations of oxidized LDL may play a role in the high incidence of coronary artery disease in gout. In addition, allopurinol may be more preferable to benzbromarone for treatment of gout in light of its inhibitory action toward LDL oxidation.