HDL Antioxidant Research Articles

Obeticholic acid's effect on HDL function in MASH varies by diabetic status.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL-the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.

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

Obesity 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.

Impact Laying Times of Broiler Breeder Supplement with Aromatic Oils (Miarom) in drinking water on Hatchability, Maternal immunity and serum antioxidant and antioxidant Statues hatched chicks

Adding aromatic oils (Miarom) in drinking water of broiler breeder was evaluated experimentally of its effect on hatchability percentage, immunity, Lipid profile, and biochemical traits at different laying times (10:00 AM and 02:00 PM). A total of 3600 eggs of broiler breeder (Ross-308) at age 60 weeks, were collected and divided into 5 treatments of different times of egg collection and laying times as follows: (T1: General Control, T2: Control 10:00 AM, T3: Control 02:00 PM, T4: Miarom 10:00 AM and T5: Miarom 02:00 PM). Results indicated the used Miarom from Miavit company - Germany (this extract contains: 200 grams essential oils mixture such as eucalyptus oil, anise oil, thyme oil, and peppermint oil) per litter it added in drinking water 1ml/10L for 7 days. The results of this study showed (p≤0.01) increased in hatching traits percentage, chick’s antibody titer against Newcastle Disease (ND) and Infectious Bronchitis Virus (IBV) by ELISA, high-density lipoprotein HDL, total protein and glutathione GSH-Px antioxidant enzyme. Also, significantly (p≤0.01) reduced infertile eggs, triglycerides TG, total cholesterol TCH, low-density lipoprotein LDL, corticosterone hormone, and malondialdehyde antioxidant enzyme. In conclusion, results showed that aromatic oils supplementation in broiler breeders leads to improve hatchability and immune status at different laying times, noticed that both Miarom treatments had a positive effect on studied parameters and T4 10:00 AM laying time was most effective in all parameters of the study.&#x0D; &#x0D;

Reduced antioxiadant high-density lipoprotein function in patients with acute coronary syndrome

Abstract Background High-density lipoprotein (HDL) function rather than concentration plays an important role in the pathogenesis of cardiovascular diseases associated with oxidative stress and inflammation such as coronary artery disease (CAD). In the last years, inflammation has been identified to have a pivotal role in the pathogenesis of acute coronary syndrome (ACS). Purpose The aim of the present study is to determine whether reduced antioxidant function of HDL is associated with ACS. Methods 197 patients with ACS were prospectively recruited and blood samples were taken in the first 48h after enrollment. Patients with chronic coronary syndrome CCS (n=727) and with invasively excluded CAD (no CAD, n=498) from another cohort from our group served as control patients. A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased HDL-lipid peroxide content (HDLox) normalized by HDL-C levels and the mean value of a pooled serum control from healthy participants (nHDLox; no units). Results Patients with ACS had significantly increased HDLox blood levels compared to patients with CCS and to patients without CAD (p&amp;lt;0.001, Figure 1A). Prior intake of statins did not influenc the differences of HDLox among the groups (Figure 1B). In the regression analysis increased HDLox was a strong risk factor for the presence of ACS compared to CCS (odds ratio 4.09 (2.98–5.62), p&amp;lt;0.001, Figure 2). Conclusions HDL peroxidation is associated with the presence of ACS independent of the presence of other traditional risk factors. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): BIOX

Optimization enzymatic degradation of chitosan into amphiphilic chitooligosaccharides for application in mitigating liver steatosis and cholesterol regulation

In our endeavor targeting enhancement of the biological activities (anti-cholesterol, anti-inflammatory, antioxidant, hepatoprotective) of chitosan; novel amphiphilic chitooligosaccharides (ACOSs) were synthesized by the enzymatic degradation of shrimp chitosan in aqueous ionic liquid to obtain COS followed by quaternization with Glycidylammonium chlorides (GAC). The capacity of COS architectures to dominate cholesterol accumulation in the liver and mitigate its consequences (steatosis and nonalcoholic fatty liver disease (NAFLD)) were in vivo investigated in rats. Our results revealed a significant reduction in the HDL level and antioxidant parameters SOD and GSH accompanied with unregulated inflammatory factor TNF-α and RBP-4 in the rats group induced by CCl4 and the AST/ALT ratio was 0.67. Interestingly, treatment with COS architectures showed significant amelioration in the antioxidant parameters, increased level of HDL, while decreased cholesterol and triglycerides in the hepatocytes (P < 0.01); overall ameliorate hepatocytes architecture. Moreover, they can significantly diminish the inflammatory factor TNF-α, LDL, and TG content in the liver homogenates of the rats (P < 0.05).

Perioperative high density lipoproteins, oxidative stress, and kidney injury after cardiac surgery

Oxidative stress promotes acute kidney injury (AKI). Higher HDL cholesterol concentrations are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle (HDL-P) size and number, paraoxonase-1 (PON-1) activity, and isofuran concentrations in 75 patients who developed AKI and 75 matched control patients. Higher preoperative HDL-P was associated with less AKI (OR: 0.80; 95% CI, 0.71–0.91; P = 0.001), higher PON-1 activity ( P < 0.001), and lower plasma concentrations of isofurans immediately after surgery (P = 0.02). Similarly, higher preoperative small HDL-P was associated with less AKI, higher PON-1 activity, and lower isofuran concentrations. Higher intraoperative particle losses were associated with less AKI (OR: 0.79; 95% CI 0.67–0.93; P = 0.005), and with decreased postoperative isofuran concentrations (P = 0.04) . Additionally, higher preoperative small HDL-P and increased intraoperative small particle loss were associated with improved long-term renal function (P = 0.003, 0.01, respectively). In conclusion, a higher preoperative concentration of HDL-P, particularly small particles, is associated with lower oxidative damage and less AKI. Perioperative changes in HDL-P concentrations are also associated with AKI. Small HDL-P may represent a novel modifiable risk factor for AKI.

Whole egg consumption compared with yolk-free egg increases the cholesterol efflux capacity of high-density lipoproteins in overweight, postmenopausal women

Postmenopausal women are at higher risk for cardiovascular disease (CVD) than their younger counterparts. HDL cholesterol is a biomarker for CVD risk, but the function of HDL may be more important than HDL cholesterol in deciphering disease risk. Although diet continues to be a cornerstone of treatment and prevention of CVD, little is known about how diet affects the functionality of HDL. The aim of this study was to characterize the effects of whole eggs compared with yolk-free eggs on HDL function and composition in overweight, postmenopausal women and determine how changes in HDL composition are related to HDL functional parameters. The study was a 14-wk, single-blind, randomized crossover dietary trial with two 4-wk intervention periods in 20 overweight, postmenopausal women. The crossover treatments were frozen breakfast meals containing 100 g of liquid (∼2) whole eggs compared with 100 g of (∼2) yolk-free eggs per day, separated by a 4-wk washout. Fasting blood samples were taken at the beginning and end of each treatment period to determine the effects on HDL composition and function. Cholesterol efflux capacity increased in the whole-egg treatment (mean ± SD percentage change: +5.69% ± 9.9%) compared with the yolk-free egg treatment (-3.69% ± 5.3%) (P<0.01), but there were no other significant changes in HDL functions or antioxidant or inflammatory markers. ApoA-I, total cholesterol (TC), LDL cholesterol, and HDL cholesterol also did not change in response to the egg treatment. The consumption of 2 whole eggs/d by overweight, postmenopausal women showed a significant increase in cholesterol efflux capacity. This increase in cholesterol efflux capacity was seen without significant changes in apoA-I, TC, LDL cholesterol, or HDL cholesterol, supporting the idea that HDL function rather than HDL cholesterol should be addressed in this population. This trial was registered at clinicaltrials.gov as NCT02445638.

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.

Association of Serum Paraoxonase/Arylesterase Activity With All-Cause Mortality in Maintenance Hemodialysis Patients.

In end-stage renal disease (ESRD), serum high-density lipoprotein cholesterol (HDL-C) level is not an accurate predictor of mortality, partly because it does not necessarily correlate with indices of HDL function. Paraoxonase (PON) is a major enzyme constituent of HDL and a key component of HDL antioxidant activity. Apolipoprotein A-I (Apo A-1) is the core HDL structural protein that plays a major role in various aspects of HDL function. We sought to examine PON activity and Apo A-I levels in patients with ESRD vs healthy controls. PON/arylesterase activity was measured in 499 patients with maintenance hemodialysis (MHD) and 24 healthy controls with similar distributions of age, sex, and race/ethnicity. Serum acrolein-modified Apo A-I was measured in 30 patients with MHD and 10 healthy controls. Multilevel Cox models were used to assess associations among PON activity, Apo A-I, and HDL-C levels with 12-month all-cause mortality. PON activity was significantly lower in patients with MHD vs controls. Furthermore, acrolein-modified Apo A-I levels were higher in patients with MHD vs controls. In fully adjusted models, high PON activity was associated with lower 12-month mortality, whereas no difference of mortality risk was observed across HDL-C levels. The combination of high PON and low Apo A-I compared with low PON and low Apo A-I was associated with lower mortality risk. In patients with MHD, PON activity had a stronger association with 12-month mortality than HDL-C. Future studies are needed to examine the role of these markers as potential diagnostic and therapeutic tools in ESRD.

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. .

Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein.

Low high-density lipoprotein cholesterol (HDL-C) levels are one of the most powerful independent negative predictors of atherosclerotic cardiovascular disease (CVD). The structure and function of HDL rather than HDL-C may more accurately predict atherosclerosis. Several HDL protein and lipid compositional changes that impair HDL function occur in inflammatory states such as atherosclerosis. HDL function is usually determined by cell based assays such as cholesterol efflux assay but these assays have numerous drawbacks lack of standardization. Cell-free assays may give more robust measures of HDL function compared to cell-based assays. HDL oxidation impairs HDL function. HDL has a major role in lipid peroxide transport and high amount of lipid peroxides is related to abnormal HDL function. Lipid-probe interactions should be considered when interpreting the results of non-enzymatic fluorescence assays for measuring the lipid oxidative state. This motivated us to develop a cell-free biochemical enzymatic method to assess HDL lipid peroxide content (HDLox) that contributes to HDL dysfunction. This method is based on the enzyme horseradish peroxidase (HRP) and the fluorochrome Amplex Red that can quantify (without cholesterol oxidase) the lipid peroxide content per mg of HDL-C. Here a protocol is describedfor determination of HDL-lipid peroxidation using the fluorochrome reagent. Assay variability can be reduced by strict standardization of experimental conditions. Higher HDLox values are associated with reduced HDL antioxidant function. The readout of this assay is associated with readouts of validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction, and associated cardiovascular and metabolic risk phenotypes. This technical approach is a robust method to assess HDL function in human disease where systemic inflammation, oxidative stress and oxidized lipids have a key role (such as atherosclerosis).

Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein

Low high-density lipoprotein cholesterol (HDL-C) levels are one of the most powerful independent negative predictors of atherosclerotic cardiovascular disease (CVD). The structure and function of HDL rather than HDL-C may more accurately predict atherosclerosis. Several HDL protein and lipid compositional changes that impair HDL function occur in inflammatory states such as atherosclerosis. HDL function is usually determined by cell based assays such as cholesterol efflux assay but these assays have numerous drawbacks lack of standardization. Cell-free assays may give more robust measures of HDL function compared to cell-based assays. HDL oxidation impairs HDL function. HDL has a major role in lipid peroxide transport and high amount of lipid peroxides is related to abnormal HDL function. Lipid-probe interactions should be considered when interpreting the results of non-enzymatic fluorescence assays for measuring the lipid oxidative state. This motivated us to develop a cell-free biochemical enzymatic method to assess HDL lipid peroxide content (HDLox) that contributes to HDL dysfunction. This method is based on the enzyme horseradish peroxidase (HRP) and the fluorochrome Amplex Red that can quantify (without cholesterol oxidase) the lipid peroxide content per mg of HDL-C. Here a protocol is describedfor determination of HDL-lipid peroxidation using the fluorochrome reagent. Assay variability can be reduced by strict standardization of experimental conditions. Higher HDLox values are associated with reduced HDL antioxidant function. The readout of this assay is associated with readouts of validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction, and associated cardiovascular and metabolic risk phenotypes. This technical approach is a robust method to assess HDL function in human disease where systemic inflammation, oxidative stress and oxidized lipids have a key role (such as atherosclerosis).

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.

Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial

BackgroundSodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce glucose levels, body weight, and blood pressure, possibly resulting in cardiovascular protection. In phase III trials, SGLT2i were shown to increase HDL cholesterol. We aimed to evaluate whether the SGLT2i dapagliflozin affects HDL function in a randomized placebo-controlled trial.MethodsThirty-three type 2 diabetic patients were randomized to receive dapagliflozin 10 mg or placebo for 12 weeks on top of their glucose lowering medications. The primary end-point was the change in cholesterol efflux capacity (CEC) from macrophages at study end versus baseline. Secondary endpoints were changes in: distribution of HDL subfractions, lipid profile, activity of enzymes that mediate HDL antioxidant properties (PON1 and ARE) and cholesterol metabolism (CETP), HbA1c, body weight and composition.ResultsThirty-one patients completed the study, n = 16 in the placebo group and n = 15 in the dapagliflozin group. Patients randomized to dapagliflozin were older and had lower adiposity indexes, although these differences disappeared after correction for multiple testing. Therapy with dapagliflozin reduced HbA1c by 0.9% and body weight by 3.1 kg, mainly attributable to reduction of body water and lean mass. As compared to placebo, dapagliflozin reduced CEC (−6.7 ± 2.4 versus 0.3 ± 1.8%; p = 0.043), but this effect was no longer significant after adjusting for age and BMI. No change was detected in HDL cholesterol, HDL subfractions, activity of PON1, ARE, and CETP.ConclusionsDespite improvements in glucose control and reduction in body weight, therapy with dapagliflozin exerted no significant effect on HDL cholesterol levels and HDL functionality.Trial registration EudraCT 2014-004270-42; NCT02327039

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.

Association of genetic variants of pentraxin 3 rs3816527 with hypertension in Chronic kidney disease patients.

Hypertension is a nearly constant feature and both a cause and a consequence of chronic kidney disease (CKD). Atherosclerotic lesions showed a marked expression of pentraxin 3 on the surface of lumen and in the plaque. The aim was to assess the correlation of exon 2 of pentraxin 3 gene SNP rs3816527 with hypertension with CKD. The study was conducted on 110 CKD patients (60 patients with and 50 patients without hypertension) and 40 healthy subjects as control. Laboratory investigations including the measurement of fasting blood glucose, lipid profile, and indices of oxidative stress, liver function tests, and renal function tests were done. Genotyping of pentraxin 3 gene SNP rs3816527 was done by real-time PCR. There was a significant difference between CKD patients with hypertension and the subjects in the control group regarding systolic and diastolic BP, urea, creatinine, GFR, TG, cholesterol, LDL, HDL, and total antioxidant levels (p<0.001). There is a statistically significant difference between CKD patients with hypertension and the other studied groups regarding the frequencies of AA genotype and A allele of exon 2 SNP of pentraxin 3 gene compared to CC genotype and C allele (wild type) (p<0.001), while there was significant difference between CKD patients without hypertension and control (p>0.05). Pentraxin 3 AA genotype SNP rs3816527 can be considered as a potential biomarker and a risk factor for CKD patients, especially hypertensive patients, and specifically as an independent predictor of hypertension in CKD.

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.

Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1

The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1P297S heterozygotes.Lipoproteins from six SR-B1P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed.Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I.The SR-B1P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1.

Consumption of polyunsaturated fat improves the saturated fatty acid-mediated impairment of HDL antioxidant potential.

The present study aimed to compare the effects of diets containing high-fat, high-cholesterol and saturated fatty acids (HFHC-SFA) and HFHC-polyunsaturated fatty acids-containing (HFHC-PUFA) diets on two major antiatherogenic functions of HDL, the HDL antioxidant function and the macrophage-to-feces reverse cholesterol transport. Experiments were carried out in mice fed a low-fat, low-cholesterol (LFLC) diet, an HFHC-SFA diet or an HFHC-PUFA diet in which SFAs were partly replaced with an alternative high-linoleic and α-linolenic fat source. The HFHC-SFA caused a significant increase in serum HDL cholesterol and phospholipids as well as elevated levels of oxidized HDL and oxidized LDL. Replacing SFA with PUFA significantly reduced the levels of these oxidized lipoproteins and enhanced the ability of HDL to protect LDL from oxidation. The SFA-mediated impairment of HDL antioxidant potential was not associated with the cholesterol content of the diet, obesity or insulin resistance. In contrast, the effect of the HFHC diets on fecal macrophage-derived cholesterol excretion was independent of the fatty acid source. SFA intake impairs the antioxidant potential of HDL and increases serum levels of oxidized lipoprotein species whereas the antioxidant potential of HDL is enhanced after PUFA consumption.