HDL Antioxidant Capacity Research Articles

Cholesterol transfer to high‐density lipoprotein in obesity and the effects of weight loss after bariatric surgery

SummaryObesity increases serum triglycerides and decreases high‐density lipoprotein cholesterol (HDL‐C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1‐OB) and III (G3‐OB) obesity and effects of bariatric surgery on G3‐OB. Fifteen G3‐OB patients (43 ± 6 years, BMI 49 ± 3 kg/m2) were studied before and 1 year after bariatric surgery; 15 G1‐OB (32 ± 2 years, 32 ± 2 kg/m2) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m2) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3‐OB had higher triglycerides and lower HDL‐C; G1‐OB had higher triglycerides than NW but HDL‐C was equal. Compared to NW, HDL size was smaller in G3‐OB but equal in G1‐OB. One year after bariatric surgery, BMI and triglycerides of G3‐OB decreased (p < .0001 and p = .0012, respectively) and HDL‐C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3‐OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL‐C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions.

Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 modulate bile acids and cholesterol metabolism in humans.

Probiotics with high bile salt hydrolase (BSH) activity have shown to promote cardiovascular health. However, their mechanism(s) of action remain poorly understood. Here, we performed a pilot exploratory study to investigate effects of a 4-week intervention with escalating doses of a BSH-active formula containing Lactiplantibacillus plantarum strains KABP011, KABP012, and KABP013 on bile acid (BA), lipid profile, and lipoprotein function. Healthy overweight individuals were included in this study. The probiotic intake was associated with a progressive decrease of conjugated BAs in serum, due to the reduction of tauro- and glyco-conjugated forms. Plasma levels of fibroblast growth factor-19 were significantly reduced and correlated with BA changes. The probiotic induced significant changes in serum lipids, with reduction in non-HDL cholesterol (non-HDLc) and LDL cholesterol (LDLc) levels. The largest decrease was evidenced in the subgroup with higher baseline LDLc levels (LDLc > 130 mg/dL). Fasting levels of circulating apolipoprotein(Apo) B100 and ApoB48 were significantly reduced. Importantly, the decrease in non-HDLc levels was associated with a significant reduction in small LDL particles. Functional testing indicated that LDL particles had a significantly lower susceptibility to oxidation, while HDL particles gained antioxidant capacity after the probiotic intake. The microbiota profile in faeces collected at the end of the study was enriched with members of class Desulfovibrio, a taurine-consuming bacteria, likely because of the increase in free taurine in the gut due to the BSH activity of the probiotic. The intervention with L. plantarum strains induces beneficial effects on BA signature and lipoprotein profile. It reduces ApoB and small LDL levels and LDL susceptibility to oxidation and increases HDL antioxidant capacity. These metabolic profile changes suggest increased protection against atherosclerotic disease.

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

Antioxidative Effects of Rosuvastatin in Low-to-Moderate Cardiovascular Risk Subjects.

Background: Although vast clinical evidence supports the oxidative CVD hypothesis, little is known on the effects of statins on LDL/HDL oxidative functionality. Therefore, the aim of this study was to evaluate the antioxidative effects of rosuvastatin by monitoring the susceptibility of LDL to oxidation and the antioxidative HDL potential in low-to-moderate CV risk subjects. Methods: 40 adult ambulatory patients (aged 53.8±10.9 years, 27 women and 13 men) were included in the study. Data was collected from patients' records, physical examination, and blood sampling. Subjects were prescribed rosuvastatin at 20mg/day. Traditional risk-factors/indicators, lipid parameters, inflammatory/immune markers, LDL susceptibility to oxidation and HDL antioxidative potential were monitored and statistically analyzed with t-test, Chi-square test, one-way ANOVA, Mann-Whitney, and Kruskal-Wallis tests. Multivariate logistic regression analyses were made. Results were considered significant when p≤0.05. Results: 67% of the patients showed lower susceptibility of LDL to oxidation after rosuvastatin treatment (p=0.03), with no significant effect on baseline LDL oxidation and lag time. All three LDL oxidative indices were seen to be dependent on the subjects' lipid profile, hemoglobin levels and the IL-1α and IL-8 pro-inflammatory marker levels. 53% of the patients showed higher HDL antioxidative capacity after treatment, but without statistical significance (p=0.07). Increased antioxidative potential of HDL with rosuvastatin treatment was more likely in males (OR=9.350; p=0.010), and subjects achieving lower post-treatment CV relative risk levels (higher CV risk reduction) (OR=0.338; p=0.027). Conclusions: This study suggests the need of a comprehensive approach when investigating oxidative stress and LDL/HDL functions, especially in low-to-moderate CVD risk subjects.

HDL and Oxidation.

In this chapter, we will focus on HDLs' activity of inhibiting LDL oxidation and neutralizing some other oxidants. ApoA-I was known as the main antioxidant component in HDLs. The regulation of antioxidant capacity of HDL is mainly exhibited in regulation of apoA-I and alterations at the level of the HDL lipidome and the modifications of the proteome, especially MPO and PON1. HDL oxidation will influence the processes of inflammation and cholesterol transport, which are important processes in atherosclerosis, metabolic diseases, and many other diseases. In a word, HDL oxidation might be an effective antioxidant target in treatment of many diseases.

Maternal supraphysiological hypercholesterolemia is associated with increased levels of lipid peroxidation and an increased antioxidant capacity of maternal HDL, but not with changes in PON1 activity

Maternal supraphysiological hypercholesterolemia is associated with increased levels of lipid peroxidation and an increased antioxidant capacity of maternal HDL, but not with changes in PON1 activity

Identification and characterization of a rare variant in apolipoprotein A-IV, p.(V336M), and evaluation of HDL functionality in a Greek cohort with extreme HDL cholesterol levels

High-Density Lipoprotein cholesterol (HDL-C) levels do not correlate well with Coronary Artery Disease (CAD) risk, while HDL functionality affects atherogenesis and is a better prognostic marker for CAD. Often, the extreme HDL-C levels have a multigenic origin. Here, we searched for single-nucleotide polymorphisms (SNPs) in ten genes of HDL metabolism in a Greek cohort with very low (<10th percentile, n = 13) or very high (>90th percentile, n = 21) HDL-C. We also evaluated the association between HDL-C levels, HDL functionality (anti-oxidant capacity) and CAD in the subjects of this cohort. Individuals with low HDL-C levels had higher triglyceride levels, lower apoA-I levels, decreased HDL anti-oxidant capacity and higher incidence of CAD compared with individuals with control or high HDL-C levels. With next generation sequencing we identified 18 exonic SNPs in 6 genes of HDL metabolism and for selected amino acid changes we performed computer-aided structural analysis and modeling. A previously uncharacterized rare apolipoprotein A-IV variant, apoA-IV [V336M], present in a subject with low HDL-C (14 mg/dL) and CAD, was expressed in recombinant form and structurally and functionally characterized. ApoA-IV [V336M] had similar α-helical content to WT apoA-IV but displayed a small thermodynamic stabilization by chemical unfolding analysis. ApoA-IV [V336M] was able to associate with phospholipids but presented reduced kinetics compared to WT apoA-IV. Overall, we identified a rare apoA-IV variant in a subject with low HDL levels and CAD with altered biophysical and phospholipid binding properties and showed that subjects with very low HDL-C presented with HDL dysfunction and higher incidence of CAD in a Greek cohort.

Comparison of early cardiovascular risk among Brazilian and African university students

SummaryCardiovascular diseases are among the main causes of mortality worldwide, and dyslipidemia is a principal factor risk. Hence the study of biochemical markers is necessary for early diagnosis. ObjectivesEvaluate biomarkers to diagnose the risks of cardiovascular diseases in healthy Brazilian and African young adults. Design & MethodsWeight, height, waist circumference, percentage of body fat and systemic blood pressure were measured; and fasting blood samples were taken for biochemical analysis. Triglycerides, total cholesterol, HDL-c, and apolipoproteins A-I and B were measured on automated equipment using commercially available kits, in addition to the tests of antioxidant capacity of HDL and the enzymatic activity of Paraoxonase 1. ResultsAfter statistical analysis, it was found that BMI, WC, fat (%), triglycerides, ApoB/ApoA-I ratio and Vmax were higher in Brazilians, while HDL-c, ApoA-I, Lag Time, Vmax and PON1 activity were higher in Africans. In Brazilians, the ApoB/ApoA-I ratio was related to obesity factors and lipid profile, but in Africans it was related only to lipids. The antioxidant capacity of HDL and PON1 activity was better in Africans. Through independence testing, we observed an association with moderate risk of myocardial infarction with gender in Africans. In the binary logistic regression analysis, it was found that men in general – and particularly African men – have higher risk of myocardial infarction than women; Odds Ratio 2144 (CI95%: 1343–3424) and 2281 (CI95%: 1082–4811), respectively. ConclusionsThe anthropometric and biochemical parameters of Brazilians, especially men, predispose them to greater risks of cardiovascular diseases.

Impaired antioxidative activity of high-density lipoprotein is associated with more severe acute ischemic stroke

Background/aimsHigh-density lipoprotein (HDL) has important anti-atherogenic functions, including antioxidant effects. However, it is unclear whether the antioxidative activity of HDL is associated with the severity and outcome of acute ischemic stroke. We aimed to evaluate this association. MethodsWe prospectively studied 199 consecutive patients admitted with acute ischemic stroke and followed them up until discharge. We measured HDL antioxidant capacity, HDL-associated paraoxonase-1 (PON1) activity and HDL-associated myeloperoxidase (MPO) levels. Severe stroke was defined as National Institutes of Health Stroke Scale (NIHSS) at admission ≥5. Dependency was defined as modified Rankin scale at discharge between 2 and 5. ResultsPatients with severe stroke had lower HDL antioxidant capacity, higher MPO levels and higher MPO/PON1 ratio. Independent risk factors for severe stroke were female gender (RR 2.80, 95% CI 1.37–5.70, p = 0.005), glucose levels (RR 1.01, 95% CI 1.0–1.02, p < 0.01) and HDL antioxidant capacity (RR 1.03, 95% CI 1.01–1.06, p < 0.05). Patients who were dependent at discharge had lower HDL antioxidant capacity, higher MPO levels and higher MPO/PON1 ratio. Independent predictors of dependency at discharge were lack of lipid-lowering treatment (RR 6.86, 95% CI 1.83–25.67, p < 0.005) and NIHSS (RR 1.56, 95% CI 1.29–1.88, p < 0.0001). The HDL antioxidant capacity did not differ between patients who died during hospitalization and those who were discharged. The only independent predictor of in-hospital mortality was NIHSS (RR 1.16, 95% CI 1.06–1.27, p < 0.005). ConclusionsImpaired antioxidative activity of HDL is associated with more severe acute ischemic stroke and might also predict a worse functional outcome in these patients.

Vitamin E supplementation improves high-densitiy lipoprotein and endothelial functions in end-stage kidney disease patients undergoing hemodialysis .

Patients with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) have been shown to be at increased risk for cardiovascular disease (CVD). Decreased high-density lipoprotein cholesterol (HDL-C) and impaired cholesterol efflux capacity (CEC) have been reported in such patients, and effects of vitamin E supplementation on HDL functions are poorly understood. Therefore, the present study aimed to investigate effects of vitamin E supplementation on HDL and endothelial functions in ESKD patients undergoing HD. We also assessed the influence of diabetes and haptoglobin (Hp) phenotype on the effects of vitamin E. Vitamin E (300mg daily) was supplemented for 12weeks, followed by a 10-week washout phase in 40 ESKD patients undergoing HD (20 diabetic and 20 nondiabetic patients). HDL functions, including CEC, antioxidant capacity, and anti-inflammatory activity, were investigated. In diabetic patients, endothelial function, as represented by flow-mediated vasodilatation (FMD), was also assessed. The findings were compared according to diabetic condition or Hp phenotype. Vitamin E significantly increased CEC, whereas antioxidant capacity and anti-inflammatory activity remained unchanged. Further, the improvement in CEC was maintained after the 10-week washout phase. Endothelial function was significantly improved in diabetic patients. Subanalyses based on diabetes or Hp phenotype revealed that neither diabetes nor Hp phenotype influenced the effects of vitamin E. In ESKD patients undergoing hemodialysis, vitamin E supplementation significantly improved the HDL function of CEC and, in diabetic patients, endothelial function. These effects were independent of Hp phenotype. .

Activity of the antioxidant enzyme paraoxonase in Argentinean children living at high altitude

ABSTRACTBackground: Children living at high altitude in San Antonio de los Cobres (SAC), Argentina, were shown to have lower high-density lipoprotein cholesterol (HDL-C) levels than Buenos Aires (BA) children. HDL antioxidant capacity is mainly attributed to paraoxonase1 (PON1).Objective: To compare PON1 activity in indigenous SAC vs. BA children.Methods: A cross-sectional study compared 158 SAC vs. 97 BA children (6–16 years). Anthropometric data and lipoprotein profile were measured. PON1 was evaluated employing paraoxon (PON) and phenylacetate (ARE) activity.Results: The prevalence of overweight/obesity was lower in SAC than in BA children (18.3 vs. 30.9%). Triglycerides (1.34 vs. 0.90 mmol/l), apo B (0.84 vs.0.72 g/l), apo A-I (1.33 vs. 1.27 g/l), and ARE activity (100 vs. 90 µmol/ml/min) were higher, while HDL-C (1.16 vs. 1.32 mmol/l) and PON activity (170 vs. 203 nmol/ml/min) were lower in SAC than in BA. Separate multiple linear regression analyses showed that SAC children had significantly higher triglyceride (Beta −0.38), apo B (Beta −0.34), and ARE (Beta −0.36) plus lower HDL-C (Beta 0.33) and PON (Beta 0.25) compared with BA; adjusted for age, gender, and BMI.Conclusion: SAC showed an unfavorable lipoprotein profile, lower PON and higher ARE activities compared with BA children, suggesting the presence of altered HDL metabolism and antioxidant capacity.

Influence of HDL particles on cell-cholesterol efflux under various pathological conditions

It has been reported that low cell-cholesterol efflux capacity (CEC) of HDL is an independent risk factor for CVD. To better understand CEC regulation, we measured ABCA1- and scavenger receptor class B type I (SR-BI)-dependent cell-cholesterol efflux, HDL anti-oxidative capacity, HDL particles, lipids, and inflammatory- and oxidative-stress markers in 122 subjects with elevated plasma levels of triglyceride (TG), serum amyloid A (SAA), fibrinogen, myeloperoxidase (MPO), or β-sitosterol and in 146 controls. In controls, there were strong positive correlations between ABCA1-dependent cholesterol efflux and small preβ-1 concentrations (R2 = 0.317) and SR-BI-dependent cholesterol efflux and large (α-1 + α-2) HDL particle concentrations (R2 = 0.774). In high-TG patients, both the concentration and the functionality (preβ-1 concentration-normalized ABCA1 efflux) of preβ-1 particles were significantly elevated compared with controls; however, though the concentration of large particles was significantly decreased, their functionality (large HDL concentration-normalized SR-BI efflux) was significantly elevated. High levels of SAA or MPO were not associated with decreased functionality of either the small (preβ-1) or the large (α-1 + α-2) HDL particles. HDL anti-oxidative capacity was negatively influenced by high plasma β-sitosterol levels, but not by the concentrations of HDL particles, TG, SAA, fibrinogen, or MPO. Our data demonstrate that under certain conditions CEC is influenced not only by quantitative (concentration), but also by qualitative (functional) properties of HDL particles.

Intake of up to Three Eggs per Day is Associated with Improvements in Markers of HDL Function and Antioxidant Capacity in a Young, Healthy Population

Recent evidence suggests that the composition and function of HDL particles may be more important than HDL cholesterol concentration when assessing risk for cardiovascular disease (CVD). HDL is involved in reverse cholesterol transport, the process by which excess cholesterol is removed from tissues and returned to the liver for biliary excretion. In addition to transporting cholesterol, HDL particles carry antioxidant proteins, enzymes, and carotenoids, all of which help protect against oxidative damage to both HDL and LDL particles. Eggs contain cholesterol and carotenoids and therefore may impact CVD risk by modulating lipoprotein composition and function. The goal of this research was to determine the impact of intake of up to 3 eggs/d on LDL and HDL particle size, function, and associated antioxidants in a young, healthy population. Thirty‐eight healthy individuals (19 men/19 women, 24.1 ± 2.2 y, BMI 24.3 ± 2.5 kg/m2) completed this 14‐week crossover dietary intervention. Qualifying participants underwent a 2‐week washout (0 eggs/d), followed by intake of 1, 2, and 3 eggs/d for 4 weeks each. Following each dietary period, fasting plasma and serum were collected for analysis of lipoprotein particle size and subfractions by nuclear magnetic resonance and concentrations of plasma apolipoproteins and carotenoids (lutein and zeaxanthin). Activities of plasma cholesteryl ester transfer protein (CETP) and lecithin‐cholesterol acyltransferase (LCAT) were assessed using fluorometric kinetic assays. Lastly, serum paraoxonase‐1 (PON1) activity toward phenyl acetate was measured using an in‐house kinetic assay. Compared to 0 eggs/d, intake of 1–3 eggs/d led to increased large LDL and large HDL particle concentrations (p &lt; 0.05), a 9–20% increase in plasma apoA‐I (p &lt; 0.05), and increased LCAT activity (p &lt; 0.05). Furthermore, as compared to 0–1 eggs/d, intake of 2–3 eggs/d resulted in an 11% increase in apoA‐II (p &lt; 0.05) and a 20–31% increase in plasma lutein + zeaxanthin (p &lt; 0.05). Lastly, as compared to lesser quantities of eggs, intake of 3 eggs/d led to increased serum PON1 activity (p &lt; 0.05). In contrast, egg intake had no impact on plasma CETP activity. In summary, intake of 1 egg/d appears sufficient to increase large LDL particle concentration and biomarkers associated with HDL function. However, intake of 2–3 eggs/d supports greater improvements in markers of HDL function and antioxidant capacity. Overall, intake of up to 3 eggs/d improves these biomarkers associated with lipoprotein function and CVD risk in a young, healthy population.Support or Funding InformationThis research was supported by an award to MLF from the Esperance Family Foundation and a grant to DMD from the Egg Nutrition Center.

High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration.

PurposeHigh-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients.MethodsBlood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants.ResultsIn our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01).ConclusionsThe investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis.

High-density lipoprotein function in rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis despite the appearance of having a less atherogenic lipid profile; however, lipoprotein function rather than concentration may be a better indicator of atherosclerotic risk. The purpose of this review is to summarize recent findings concerning HDL function in patients with RA. Two major activities of HDL, its antioxidant and cholesterol efflux functions have been examined in RA. HDL antioxidant capacity is inversely associated with inflammation and RA disease activity; however, there is no clear consensus if antioxidant capacity is altered significantly in RA compared with control study participants. Moreover, despite numerous studies there is no consensus whether HDL cholesterol efflux capacity is significantly altered in RA compared with control study participants or influenced by inflammation or disease activity. Additional studies will be valuable to consolidate existing data and find consensus. Moreover, studies evaluating the impact of various HDL functions on cardiovascular disease in RA are needed.

Effects of urban fine particulate matter and ozone on HDL functionality

BackgroundExposures to ambient particulate matter (PM) are associated with increased morbidity and mortality. PM2.5 (<2.5 μm) and ozone exposures have been shown to associate with carotid intima media thickness in humans. Animal studies support a causal relationship between air pollution and atherosclerosis and identified adverse PM effects on HDL functionality.We aimed to determine whether brief exposures to PM2.5 and/or ozone could induce effects on HDL anti-oxidant and anti-inflammatory capacity in humans.MethodsSubjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 μg/m3, ozone targeted at 240 μg/m3 (120 ppb), PM2.5 plus ozone targeted at similar concentrations, and filtered air (FA) for 2 h, on 4 different occasions, at least two weeks apart, in a randomized, crossover study. Blood was obtained before exposures (baseline), 1 h after and 20 h after exposures. Plasma HDL anti-oxidant/anti-inflammatory capacity and paraoxonase activity were determined. HDL anti-oxidant/anti-inflammatory capacity was assessed by a cell-free fluorescent assay and expressed in units of a HDL oxidant index (HOI). Changes in HOI (ΔHOI) were calculated as the difference in HOI from baseline to 1 h after or 20 h after exposures.ResultsThere was a trend towards bigger ΔHOI between PM2.5 and FA 1 h after exposures (p = 0.18) but not 20 h after. This trend became significant (p <0.05) when baseline HOI was lower (<1.5 or <2.0), indicating decreased HDL anti-oxidant/anti-inflammatory capacity shortly after the exposures. There were no significant effects of ozone alone or in combination with PM2.5 on the change in HOI at both time points. The change in HOI due to PM2.5 showed a positive trend with particle mass concentration (p = 0.078) and significantly associated with the slope of systolic blood pressure during exposures (p = 0.005).ConclusionsBrief exposures to concentrated PM2.5 elicited swift effects on HDL anti-oxidant/anti-inflammatory functionality, which could indicate a potential mechanism for how particulate air pollution induces harmful cardiovascular effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0139-3) contains supplementary material, which is available to authorized users.

Effects of extremely low frequency electromagnetic fields on paraoxonase serum activity and lipid peroxidation metabolites in rat.

BackgroundAtherogenic effects of ELF-MF exposure have not been studied well so far. Therefore we have hypothesized that ELF-MF exposure might have atherogenic effect by impairing antioxidant function and increasing lipid peroxidation. This study was therefore undertaken to examine the effects of ELF-MF on paraoxonase (PON) activity, antioxidant capacity and lipid peroxidation metabolites. Effects of time on remodeling of antioxidant system were also investigated in this study.MethodsSeventy five Wistar rats were randomly allocated into five groups as follows: 1) Sham exposure, 2) Single exposure to 60 Hz, sacrificed immediately after exposure, 3) Single exposure to 60 Hz, sacrificed 72 hours after exposure, 4) Fourteen days of exposure to 60 Hz, sacrificed immediately after exposure, and 5) Fourteen days of exposure to 60 Hz, sacrificed 72 hours after exposure. Blood samples were collected and analyzed. The results were compared using ANOVA and post hoc Tukey HSD for multiple caparisons.ResultsSingle ELF-MF exposure significantly increased lipid peroxidation (CD and MDA) and increased antioxidant serum activity (HDL, paraoxonase activity, and serum total antioxidant capacity). Chronic ELF-MF exposure increased lipid peroxidation and affected antioxidant system. Free fatty acids levels were significantly increased after both single and two weeks exposure. Chronic exposure led to irreversible changes while acute exposure tended to reversible alterations on above mentioned parameters.ConclusionsAccording to the results of this study, ELF-MF exposure could impair oxidant-antioxidant function and might increase oxidative stress and lipid peroxidation. Antioxidant capability was dependent on the duration and continuity of ELF-MF exposure.

HDL anti-oxidant function associates with LDL level in young adults

ObjectivesThe primary objective was to evaluate predictors of HDL anti-oxidant function in young adults. BackgroundHigh-density lipoprotein (HDL) cholesterol is considered a protective factor for cardiovascular disease (CVD). However, increased levels are not always associated with decreased cardiovascular risk. A better understanding of the importance of HDL functionality and how it affects CVD risk is needed. MethodsFifty non-Hispanic white subjects from the Testing Responses on Youth (TROY) study were randomly selected to investigate whether differences in HDL anti-oxidant function are associated with traditional cardiovascular risk factors, including carotid intima media thickness (CIMT), arterial stiffness and other inflammatory/metabolic parameters. HDL anti-oxidant capacity was evaluated by assessing its ability to inhibit low-density lipoprotein (LDL) cholesterol oxidation by air using a DCF-based fluorescent assay and expressed as a HDL oxidant index (HOI). The associations between HOI and other variables were assessed using both linear and logistic regression. ResultsEleven subjects (25%) had an HOI ≥ 1, indicating a pro-oxidant HDL. Age, LDL, high sensitivity C-reactive protein (hsCRP), and paraoxonase activity (PON1), but not HDL, were all associated with HOI level in univariate linear regression models. In multivariate models that mutually adjusted for these variables, LDL remained the strongest predictor of HOI (0.13 increase in HOI per 1 SD increase in LDL, 95% CI 0.04, 0.22).Atherogenic index of plasma, pulse pressure, homocysteine, glucose, insulin, CIMT and measurements of arterial stiffness were not associated with HOI in this population. ConclusionsThese results suggest LDL, hsCRP and DBP might predict HDL anti-oxidant function at an early age.

Anti‐oxidative and cholesterol efflux capacities of high‐density lipoprotein are reduced in ischaemic cardiomyopathy

Various pathological changes lead to the development of heart failure (HF). HDL is dysfunctional in both acute coronary syndrome, as measured by the HDL inflammatory index (HII) assay, and stable coronary disease, as measured by cholesterol efflux capacity. We therefore hypothesized that these functions of HDL are also impaired in subjects with ischaemic cardiomyopathy. A case-control study was performed on subjects in the University of Pennsylvania Catheterization Study (PennCath) cohort of patients with angina. Cases had EF <50% and angiographic CAD (≥70% stenosis of any vessel; n = 23); controls included those with EF ≥55% and no CAD (n = 46). Serum from subjects was apolipoprotein-B depleted to isolate an HDL fraction. To measure HDL anti-oxidative capacity, the HDL fraction was incubated with LDL and a reporter lipid that fluoresces when oxidized. To measure cholesterol efflux capacity, the HDL fraction was also incubated with macrophages and tritium-labelled cholesterol. Mean HII was higher and efflux capacity lower in subjects with ischaemic cardiomyopathy (HII 0.26 vs. -0.028; efflux 0.80 vs. 0.92; P < 0.05). In a multivariable logistic regression model, both high HII and low efflux capacity were significant risk factors for HF [HII odds ratio (OR) 2.8, 95% confidence interval (CI) 2.0-3.9, P = 0.002; efflux OR 2.1, 95% CI 1.5-3.0, P = 0.03]. These effects persisted after adjustment for covariates and traditional risk factors for HF. Subjects with reduced EF from ischaemia have lower HDL concentration and also impaired HDL function. HDL is a versatile lipoprotein particle with various anti-inflammatory and vasoprotective functions, whose impairment may contribute to ischaemic heart failure.

Low normal free T4 confers decreased high‐density lipoprotein antioxidative functionality in the context of hyperglycaemia

Low normal thyroid function may promote the development of atherosclerotic cardiovascular disease by thus far poorly defined mechanisms. We tested the impact of thyroid function on HDL antioxidative capacity, a metric of its antiatherogenic functionality, in euthyroid subjects with varying degrees of glucose tolerance. Seventy subjects with Type 2 diabetes mellitus (T2DM), 37 subjects with impaired fasting glucose (IFG) and 31 subjects with normal fasting glucose (NFG) (revised NCEP-ATPIII criteria) participated in a cross-sectional study. HDL antioxidative capacity (standardized for HDL cholesterol) was measured as the percentage inhibition of low-density lipoprotein oxidation in vitro. TSH, free T4 and HDL antioxidative capacity were not different among NFG, IFG and T2DM subjects (P > 0·25 for each). HDL antioxidative capacity was correlated positively with free T4 (r = 0·320, P = 0·007), and negatively with plasma glucose (r = -0·394, P < 0·001) in T2DM only. Taking account of age and sex, the relationship of HDL antioxidative functionality with free T4 was modified by glucose tolerance status (P = 0·040 and P = 0·008 for interactions of IFG and T2DM with free T4 respectively). Prevailing plasma glucose also interacted positively with free T4 on HDL antioxidative capacity (P = 0·054). In the context of chronic hyperglycaemia, low free T4 within the euthyroid range confers diminished HDL antioxidative capacity, a pathophysiologically relevant metric of HDL functionality.