Improving Assessment of Lipoprotein Profile in Type 1 Diabetes by 1H NMR Spectroscopy

Patients with type 1 diabetes (T1D) present increased risk of cardiovascular disease (CVD). The aim of this study is to improve the assessment of lipoprotein profile in patients with T1D by using a robust developed method 1H nuclear magnetic resonance spectroscopy (1H NMR), for further correlation with clinical factors associated to CVD. Thirty patients with T1D and 30 non-diabetes control (CT) subjects, matched for gender, age, body composition (DXA, BMI, waist/hip ratio), regular physical activity levels and cardiorespiratory capacity (VO_2peak), were analyzed. Dietary records and routine lipids were assessed. Serum lipoprotein particle subfractions, particle sizes, and cholesterol and triglycerides subfractions were analyzed by 1H NMR. It was evidenced that subjects with T1D presented lower concentrations of small LDL cholesterol, medium VLDL particles, large VLDL triglycerides, and total triglycerides as compared to CT subjects. Women with T1D presented a positive association with HDL size (p<0.005; R = 0.601) and large HDL triglycerides (p<0.005; R = 0.534) and negative (p<0.005; R = -0.586) to small HDL triglycerides. Body fat composition represented an important factor independently of normal BMI, with large LDL particles presenting a positive correlation to total body fat (p<0.005; R = 0.505), and total LDL cholesterol and small LDL cholesterol a positive correlation (p<0.005; R = 0.502 and R = 0.552, respectively) to abdominal fat in T1D subjects; meanwhile, in CT subjects, body fat composition was mainly associated to HDL subclasses. VO_2peak was negatively associated (p<0.005; R = -0.520) to large LDL-particles only in the group of patients with T1D. In conclusion, patients with T1D with adequate glycemic control and BMI and without chronic complications presented a more favourable lipoprotein profile as compared to control counterparts. In addition, slight alterations in BMI and/or body fat composition showed to be relevant to provoking alterations in lipoproteins profiles. Finally, body fat composition appears to be a determinant for cardioprotector lipoprotein profile.     

Oxidized low-density lipoprotein (oxLDL) plasma levels and oxLDL to LDL ratio — Are they real oxidative stress markers in dialyzed patients?

AimsDyslipidemia and oxidative stress are commonly present in patients during maintenance dialysis treatment. However, the significance of oxidized LDL (oxLDL) as a marker of oxidative stress in uremia is still unresolved. The aim of this study was to establish the role of oxLDL and oxLDL/LDL ratio as markers of lipoprotein abnormalities and oxidative stress in the dialyzed patients.Main methodsPlasma oxLDL level was measured by ELISA, and oxLDL/LDL ratio was calculated in 106 dialyzed patients and 20 controls. The linkages between oxLDL, oxLDL/LDL ratio and lipid profile and oxidative stress markers malondialdehyde (MDA) and Cu/Zn superoxide dismutase (Cu/Zn SOD) levels were also analyzed.Key findingsOxLDL levels and oxLDL/LDL ratio were similar in hemodialyzed patients and controls, whereas these parameters were lower in peritoneally dialyzed patients when compared to healthy individuals. In contrast, both MDA and Cu/Zn SOD levels were significantly higher in uremics than in controls. oxLDL and oxLDL/LDL ratio positively correlated with lipid profile (except of HDL), whereas there were no positive associations between these parameters and both MDA and Cu/Zn SOD. Multiple regression analysis confirmed that increased oxLDL/HDL and TC/HDL ratios and total cholesterol levels are the parameters which independently predicted oxLDL in dialyzed patients. In the case of oxLDL/LDL ratio, the independent variables were oxLDL/HDL ratio, total cholesterol and HDL levels.SignificanceoxLDL levels and oxLDL/LDL ratio seem to be the markers of lipoprotein abnormalities rather than the markers of oxidative stress in the population of dialyzed patients.     

Evaluation of low density lipoprotein oxidation in a course of hypothyroidism

INTRODUCTION: The aim of this study was to evaluate the influence of hypothyroidism on oxidative modification of low density lipoprotein (LDL). MATERIAL AND METHODS: 24 patients with overt hypothyroidism and 10 patients with mild hypothyroidism were enrolled to the study. The control group consisted of 24 healthy subjects with normal serum TSH. Plasma level of oxidized LDL (oxLDL) and serum level of antibodies against oxidized LDL (anti-oxLDL) determined lipoprotein oxidation. RESULTS: Significantly increased plasma oxLDL levels were found in patients with overt hypothyroidism in comparison to patients with mild hypothyroidism and control group. Anti-oxLDL levels in patients with overt or mild hypothyroidism and in the control group showed no significant differences. OxLDL plasma levels in patients with hypothyroidism inversely correlated with FT(4) levels and positively correlated with TSH, total cholesterol, LDL cholesterol and triglycerides levels. CONCLUSIONS: The presented study indicates increased lipoprotein oxidation in patients with hypothyroidism which depends on the degree of hypothyroidism and changes in lipid profile. Elevated cholesterol and triglycerides levels are the factors increasing lipoprotein oxidation. Plasma oxLDL levels may constitute a useful marker indicating the risk for atherosclerosis in hypothyroidism.     

The protective effects of HDL and its constitutents against neutrophil respiratory burst activation by hypochlorite-oxidized LDL

Hypochlorite-oxidized low-density lipoprotein (oxLDL) possesses a substantial proinflammatory potential by modulating respiratory burst activities of polymorphonuclear neutrophils (PMN). As evaluated by luminol-amplified chemiluminescence (CL) incubation of 10(6) PMN/ml with 70 nM oxLDL was followed by substantial induction of neutrophil oxidant (ROS) generation. We evaluated the inhibitory capacity of high-density lipoprotein (HDL) and its lipid and protein constituents against the activating effects of oxLDL. At a HDL or apolipoprotein AI/LDL protein ratio of 1.0, native HDL decreased the respiratory burst activation by 64%, followed by trypsinized HDL (57%) and native apoAI (43%). The inhibitory effects of native HDL did not require prior incubation with PMN or with oxLDL suggesting an instantaneously acting protective mechanism in the minute range. OxLDL modulated ROS production not only of resting PMN but also that of activated PMN, as indicated by a 14-fold increase in FMLP-stimulated CL response and a 50% decrease in zymosan-mediated CL answer. HDL itself did not protect PMN from activation by FMLP and zymosan. However, it clearly reduced effects of oxLDL on FMLP-activation and slightly counteracted the oxLDL-mediated decrease in zymosan-induced ROS generation. Taken together, these findings may offer new insight into atheroprotective mechanisms of HDL.     

Castelli risk indexes 1 and 2 are higher in major depression but other characteristics of the metabolic syndrome are not specific to mood disorders

Aims

This study examined whether Castelli risk indexes 1 (total/high-density lipoprotein (HDL) cholesterol) and 2 (low density lipoprotein (LDL)/HDL cholesterol) and other shared metabolic disorders might underpin the pathophysiology of the metabolic syndrome, major depression or bipolar disorder.

Main methods

This cross-sectional study examined 92 major depressed, 49 bipolar depressed and 201 normal controls in whom the Castelli risk indexes 1 and 2 and key characteristics of the metabolic syndrome, i.e. waist/hip circumference, body mass index (BMI), systolic/diastolic blood pressure, total cholesterol, low-density lipoprotein (LDL) and HDL cholesterol, triglycerides, insulin, glucose, hemoglobin A1c (HbA1c) and homocysteine were assessed.

Key findings

Castelli risk indexes 1 and 2 were significantly higher in major depressed patients than in bipolar disorder patients and controls. There were no significant differences in waist or hip circumference, total and LDL cholesterol, triglycerides, plasma glucose, insulin, homocysteine and HbA1c between depression and bipolar patients and controls. Bipolar patients had a significantly higher BMI than major depressed patients and normal controls.

Significance

Major depression is accompanied by increased Castelli risk indexes 1 and 2, which may be risk factors for cardiovascular disease. Other key characteristics of the metabolic syndrome, either metabolic biomarkers or central obesity, are not necessarily specific to major depression or bipolar disorder.     

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.     

Effects of oxidized low-density lipoproteins on the hepatic microvasculature

Oxidized low-density lipoproteins (oxLDLs) are involved in proinflammatory and cytotoxic events in different microcirculatory systems. The liver is an important scavenger organ for circulating oxLDLs. However, the interaction of oxLDL with the hepatic microcirculation has been poorly investigated. The present study was conducted to examine the effects of differently modified oxLDLs on the hepatic microvasculature. C57Bl/6J mice were injected intravenously with low-density lipoprotein (LDL), or LDL oxidized for 3 h (oxLDL(3)) or 24 h (oxLDL(24)), at doses resembling oxLDL plasma levels in cardiovascular disease patients. Radioiodinated ligands were used to measure blood decay and organ distribution, and nonlabeled ligands to evaluate microcirculatory responses, examined by in vivo microscopy 30-60 min after ligand injection, immunohistochemistry, and scanning and transmission electron microscopy. Mildly oxLDL (oxLDL(3)) was cleared from blood at a markedly slower rate than heavily oxLDL (oxLDL(24)), but significantly faster than LDL (P < 0.01). Injected oxLDLs distributed to liver. OxLDL effects were most pronounced in central areas of the liver lobules where oxLDL(3) elicited a significant (P < 0.05) reduction in perfused sinusoids, and both oxLDL(3) and oxLDL(24) significantly increased the numbers of swollen endothelial cells and adherent leukocytes compared with LDL (P < 0.05). OxLDL-treated livers also exhibited increased intercellular adhesion molecule (ICAM)-1 centrilobular staining. Electron microscopy showed a 30% increased thickness of the liver sinusoidal endothelium in the oxLDL(3) group (P < 0.05) and a reduced sinusoidal fenestration in centrilobular areas with increased oxidation of LDL (P for linear trend <0.05). In conclusion, OxLDL induced several acute changes in the liver microvasculature, which may lead to sinusoidal endothelial dysfunction.     

Cardiovascular risk in obese and nonobese patients with type 2 diabetes in the West Indies

OBJECTIVE: To evaluate the impact of obesity on glycemic control and the risk of progressing to cardiovascular disease (CVD) in obese and nonobese type 2 diabetic patients in primary care settings. METHODS: One hundred and ninety patients (64 men, 126 women) with type 2 diabetes (mean duration 9.2 years) were studied after an overnight fast. Weight, height, waist and hip circumferences and blood pressure were measured and blood samples were taken for glucose, glycated hemoglobin (HbA(1c)), total cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and creatinine determinations. RESULTS: About 85% of the patients had HbA(1c) levels > 7.0%, and 48% had a diastolic blood pressure (BP) >83 mm Hg, while 40% had a total cholesterol/HDL-cholesterol ratio greater than 6. The prevalence rates of hypercholesterolemia, hypertriglyceridemia, high BP and ratios of total cholesterol to HDL-cholesterol between the obese and nonobese patients were similar irrespective of sex (p > 0.05). Multiple linear regression analysis confirmed that ethnicity, sex, age and duration of diabetes had significant impact on the cardiovascular risk in this population. CONCLUSION: Both obese and nonobese diabetic patients had poor glycemic control and their risk of CVD was not independent of age, sex, ethnicity and duration of diabetes. We suggest strict metabolic control and improved diabetes health education at the primary care level.     

强化阿托伐他汀治疗对ACS患者血脂水平的短期影响

目的:观察强化阿托伐他汀治疗对急性冠脉综合征(ACS)患者血脂水平的短期影响。方法:收集100例ACS患者,入院当天(the day of admission,D0)、入院第一天(the first day,D1)及入院第二天(The Second Day,D2)分别给予阿托伐他汀80mg治疗,入院D0立即采血化验血脂参数包括总胆固醇(total cholesterol,TC)、低度脂蛋白(LDL-cholesterol,LDL-C)、高密度脂蛋白(HDL-cholesterol,HDL-C)、甘油三酯(triglycerides,TG),分别在D1和D2晨起空腹复查。结果:总胆固醇的平均基线水平为5.24±0.07(D0),低密度脂蛋白为3.26±0.07,高密度脂蛋白胆固醇为1.07±0.07,甘油三酯为1.31±0.07。口服阿托伐他汀80毫克后第一天早晨,TC水平下降6.1%(D1)(与D0相比P0.001),第二日下降13.2%(D2)(与D0相比P0.001),LDL-C下降5.8%(D1)(DO与D1相比,P0.001)和15.6%(D2)(DO与D2相比,P0.001);HDL-C下降7.5%(D1)(DO与D1相比,P0.001)和12.1(D2)(DO与D2相比,P0.001);相反TG水平升高20.6%(D1)(DO与D1相比,P0.001)和25.5%(D2)(DO与D2相比,P0.001)。结论:强化他汀治疗对ACS患者血脂短期的影响与长期的影响是不同的,TC,LDL和HDL在短期内是下降的,而TG是升高的。     

Effects of Opisthorchis viverrini infection on glucose and lipid profiles in human hosts: A cross-sectional and prospective follow-up study from Thailand

Opisthorchis viverrini (OV) infection is endemic to the Northeast Thailand where the prevalence of Type 2 Diabetes mellitus (T2DM) is higher whilst the incidence of cardiovascular diseases (CVDs) is lower than the rest of Thailand. Helminth infection has both nutritional and immunological impact on their definitive hosts. Thus, a cross-sectional study was performed to see the effects of OV infection on glucose and lipid profiles. For this purpose, 200 each of OV infected and uninfected residents were recruited and their glycated hemoglobin (HbA1c), total cholesterol, triglycerides, low- and high-density lipoproteins (LDL and HDL) levels and anthropometric measurements, including BMI were examined. Then, as the prospective follow- up study, changes of those metabolic parameters of OV positive subjects (n = 120) before and after Praziquantel (PZQ) treatment were monitored for six months. The results showed that OV infection has a protective effect against hyperglycemia (OR 0.482 and p = .04) and metabolic disease risk group (OR 0.478 and p = .03). OV positive participants had lower HbA1c (5.5% Vs. 6.01%, p = .001) but higher HDL (54.07 Vs. 49.46 mg/dL, p = .001) than OV negative participants that are statistically significant. After PZQ treatment for OV-positive subjects, their serum levels of HbA1c (p < .05) and HDL (p < .05) significantly rose during the follow up. Apparently, OV infection lowers HbA1c but increases HDL in definitive human hosts.     

Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells.

Increased levels of low-density lipoproteins are well-established risk factors of endothelial dysfunction and the metabolic syndrome. In this study, we evaluated the effect of native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) on the expression of genes of the renin-angiotensin system (angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT(1)) and their receptors (low-density lipoprotein receptor: LDLR; lectin-like oxLDL receptor: LOX-1; toll-like receptor 4: TLR4) in primary cultures of human umbilical vein endothelial cells. ACE and AT(1) expressions were significantly increased after stimulation with nLDL and oxLDL. OxLDL receptor LOX-1 showed a maximum induction after 7 hours. Increased LOX-1 protein expression in response to oxLDL could be blocked by a LOX-1-specific antibody. TLR4 expression was increased by nLDL and oxLDL as well. We conclude that LDL and oxLDL can activate the renin-angiotensin system and their receptors LDLR, LOX-1, and TLR4 in human endothelial cells. These data suggest a novel link between hypercholesterolemia and hypertension in patients with the metabolic syndrome.     

CD36 does not play a direct role in HDL or LDL metabolism

CD36 and scavenger receptor class B, type I (SR-BI) are both class B scavenger receptors that recognize a broad variety of ligands, including oxidized low density lipoprotein (oxLDL), HDL, anionic phospholipids, and apoptotic cells. In this study we investigated the role of mouse CD36 (mCD36) as a physiological lipoprotein receptor. We compared the association of various lipoprotein particles with mCD36 and mSR-BI expressed in COS cells by adenovirus-mediated gene transfer. mCD36 bound human oxLDL and mouse HDL with high affinity. Human LDL bound poorly to mCD36, indicating that mCD36 is unlikely to play a significant role in LDL metabolism. The ability of mCD36 to mediate the selective uptake of cholesteryl esters (CE) from receptor-bound HDL was assessed. In comparison with mSR-BI, mCD36 inefficiently mediated the selective uptake of CE. Hepatic overexpression of mCD36 in C57BL/6 mice by adenovirus-mediated gene transfer did not result in significant alterations in plasma LDL and HDL levels. We conclude that mCD36, while able to bind HDL with high affinity, does not contribute significantly to HDL or LDL metabolism.     

2型糖尿病患者APPL1、AFABP与胰岛素抵抗指数的相关性研究

目的:分析2型糖尿病(T2DM)患者磷酸酪氨酸衔接蛋白(APPL1)、脂肪细胞型脂肪酸结合蛋白(AFABP)与稳态模型评估胰岛素抵抗指数(HOMA-IR)的相关性。方法:选择2015年6月~2016年5月至我院就诊T2DM患者100例作为患病组,选取同期在我院健康体检者100例作为健康组,对研究对象进行指标如空腹血糖(FPG)、空腹血清胰岛素(FINS)、糖化血红蛋白(Hb A1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、APPL1、AFABP等检测,并根据公式计算HOMA-IR、及体重指数(BMI),分析APPL1、AFABP与各指标相关性。结果:患病组与健康组TC、HDL、LDL水平无明显差异(P0.05),患病组BMI、FPG、FINS、Hb A1c、TG、HOMA-IR、APPL1、AFABP与健康组比较明显较高(P0.05);APPL1与BMI、FINS、Hb A1c、HOMA-IR呈负相关性(P0.05),与FPG呈正相关性;AFABP与BMI、FPG、FINS、Hb A1c、HOMA-IR呈正相关性(P0.05)。结论:T2DM患者APPL1、AFABP较高,APPL1、AFABP与HOMA-IR呈直线相关性,表明APPL1、AFABP与T2DM患者胰岛素抵抗密切相关,该研究为APPL1、AFABP可以作为T2DM治疗的新靶点提供了理论依据。     

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), implicating oxLDL/beta2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/beta2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/beta2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/beta2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.     

Oxidized low density lipoprotein decreases macrophage expression of scavenger receptor B-I

Scavenger receptor class B type I (SR-BI) has recently been identified as a high density lipoprotein (HDL) receptor that mediates bidirectional flux of cholesterol across the plasma membrane. We have previously demonstrated that oxidized low density lipoprotein (OxLDL) will increase expression of another class B scavenger receptor, CD36 (Han, J., Hajjar, D. P., Febbraio, M., and Nicholson, A. C. (1997) J. Biol. Chem. 272, 21654-21659). In studies reported herein, we evaluated the effects of OxLDL on expression of SR-BI in macrophages to determine how exposure to this modified lipoprotein could alter SR-BI expression and cellular lipid flux. OxLDL decreased SR-BI expression in a dose- and time-dependent manner. Incubation with OxLDL had no effect on the membrane distribution of SB-BI, and it decreased expression of both cytosolic and membrane protein. Consistent with its effect on SR-BI protein expression, OxLDL decreased SR-BI mRNA in a dose-dependent manner. The ability of OxLDL to decrease SR-BI expression was dependent on the degree of LDL oxidation. OxLDL decreased both [(14)C]cholesteryl oleate/HDL uptake and efflux of [(14)C]cholesterol to HDL in a time-dependent manner. Incubation of macrophages with 7-ketocholesterol, but not free cholesterol, also inhibited expression of SR-BI. Finally, we demonstrate that the effect of OxLDL on SR-BI is dependent on the differentiation state of the monocyte/macrophage. These results imply that in addition to its effect in inducing foam cell formation in macrophages through increased uptake of oxidized lipids, OxLDL may also enhance foam cell formation by altering SR-BI-mediated lipid flux across the cell membrane.     

Cholesterol-rich low density lipoproteins are also more oxidized

Cardiovascular diseases are accompanied by active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using oxidized low-density lipoprotein (oxLDL) as a new diagnostic biomarker. Epidemiological study in populations of Estonia (782 subjects) and Russia (1433 subjects) was carried out in 2007-2009. The screening procedure included standard epidemiological methods. Oxidative stress was assessed by measuring the level of oxLDL using immunoassay method. Positive correlation between the levels of oxLDL and LDL cholesterol was indicated in blood of patients from estonian (r = 0.61; P < 0.05) and russian (r = 0.56; P < 0.05) populations. In russian population oxLDL/HDL cholesterol ratio was higher in the groups with highest risk of atherosclerosis development or manifest coronary artery disease (CAD). Cholesterol-rich low density lipoproteins are also more oxidized. Estimation of oxLDL/HDL ratio may be used as an independent biochemical marker for atherosclerosis.     

Oxidized LDL,statin use,morbidity, and mortality in patients receiving maintenance hemodialysis

Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2?±?13.8?U/L in AURORA and did not differ between treatment groups, and 74.6?±?28.1?U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.     

Uptake and fate of class B scavenger receptor ligands in HepG2 cells.

Class B scavenger receptors (SR-Bs) interact with native, acetylated and oxidized low-density lipoprotein (LDL, AcLDL and OxLDL), high-density lipoprotein (HDL3) and maleylated BSA (M-BSA). The aim of this study was to analyze the catabolism of CD36- and LIMPII-analogous-1 (CLA-1), the human orthologue for the scavenger receptor class B type I (SR-BI), and CD36 ligands in HepG2 (human hepatoma) cells. Saturation binding experiments revealed moderate-affinity binding sites for all the SR-B ligands tested with dissociation constants ranging from 20 to 30 microg.mL-1. Competition binding studies at 4 degrees C showed that HDL and modified and native LDL share common binding site(s), as OxLDL competed for the binding of 125I-LDL and 125I-HDL3 and vice versa, and that only M-BSA and LDL may have distinct binding sites. Degradation/association ratios for SR-B ligands show that LDL is very efficiently degraded, while M-BSA and HDL3 are poorly degraded. The modified LDL degradation/association ratio is equivalent to 60% of the LDL degradation ratio, but is three times higher than that of HDL3. All lipoproteins were good cholesteryl ester (CE) donors to HepG2 cells, as a 3.6-4.7-fold CE-selective uptake ([3H]CE association/125I-protein association) was measured. M-BSA efficiently competed for the CE-selective uptake of LDL-, OxLDL-, AcLDL- and HDL3-CE. All other lipoproteins tested were also good competitors with some minor variations. Hydrolysis of [3H]CE-lipoproteins in the presence of chloroquine demonstrated that modified and native LDL-CE were mainly hydrolyzed in lysosomes, whereas HDL3-CE was hydrolyzed in both lysosomal and extralysosomal compartments. Inhibition of the selective uptake of CE from HDL and native modified LDL by SR-B ligands clearly suggests that CLA-1 and/or CD36 are involved at least partially in this process in HepG2 cells.     

Vitamin A levels are decreased but not influenced by glucose- or lipid-lowering medications in subjects with type 2 diabetes

Background and aimType 2 diabetes (T2D) is a complex polygenic disease with unclear mechanisms. Clinical studies on the association of vitamin A with T2D in humans are still controversial. Herein, we aimed to investigate the plasma levels of vitamin A, predictor factors, and its correlations with clinical phenotypes in Emirati population. The effect of glucose-and lipid-lowering medications on vitamin A levels was also studied.MethodsA cross-sectional cohort comprised 158 T2D-subjects and 90 healthy controls were recruited from the United Arab Emirates National Diabetes Study (UAEDIAB). All anthropometric, clinical, and biomedical measurements were collected. Plasma levels of vitamin A were determined using ELISA assay.ResultsLevels of vitamin A were significantly lower in T2D-subjects compared to healthy control (p < 0.01). Vitamin A levels were unaffected by gender base and inversely correlated with age, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), waist circumference, triglycerides, and body mass index (BMI). Regression analysis revealed that HbA1c and age are predictors for vitamin A. Intake of glucose- or lipid-lowering medications showed no effect on vitamin A levels.ConclusionHbA1c and age are predictors for low levels of vitamin A among Emirati-T2D subjects. No influence of glucose and lipid-lowering medications on the plasma levels of vitamin A.     

Association of Serum Retinol Binding Protein 4 with Atherogenic Dyslipidemia in Morbid Obese Patients

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m²) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9±14.6; 42.3±17.0 and 37.4±11.7 µg/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL.