Lipoprotein Fractions Research Articles

Characterization of the LPS and 3OHFA Contents in the Lipoprotein Fractions and Lipoprotein Particles of Healthy Men.

Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL (p < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors.

Changes in the lipid profile of neutered cats’ blood in cases of obesity and diabetes

The aim of the present study was to examine the lipid profile, lipid fractions and the lipid peroxidation state in the blood of neutered cats with obesity and diabetes. Three groups of neutered cats (males and females) were formed for the study. We compared cats with obesity (7-9 points on a 9-point BCS scale), with obesity complicated by diabetes, and clinically healthy animals with normal body condition scores (4-5 BCS points). Lipidogram parameters, fractions of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), chylomicrons (CM), lipid peroxidation products (POL) - lipid hydroperoxides (GPL) and malondialdehyde (MDA) were analysed. In obese cats, a decrease in HDL and phospholipids was observed, and an increase in LDL, VLDL, CM, triglycerides, and cholesterol. No significant differences in lipid and lipoprotein metabolism between neutered females and males were found. A tendency towards increasing concentrations of lipoproteins, triglycerides and cholesterol in males, as well as an increase in phospholipids in females was found. In cats with obesity and associated diabetes, the ratio of phospholipids: cholesterol was less than one, while in healthy cats - more than one. Obesity and diabetes initiate POL and increased concentrations of GPL and MDA, which were the highest in the blood of females with associated pathology.

Arylesterase activity of paraoxonase 1 in patients with primary hypertension

Abstract Introduction Paraoxonase 1 is an enzyme associated with high-density lipoprotein fraction and is considered to present antioxidant activity. Objectives The aim of the study was to assess the arylesterase activity of paraoxonase 1 (PON1) in the serum of patients with hypertension, due to effect of therapy and before treatment. Patients and Methods. The study was conducted in 76 patients with primary hypertension and 28 volunteers for the control group. Hypertensive subjects were assigned to one of three groups: well controlled (n=25), poorly controlled (n=26), and newly diagnosed before therapy (n=25) hypertension. We evaluated metabolic parameters in all participants using routine laboratory methods, as well as arylesterase activity of PON1. Results The four study groups differed with arylesterase activity of PON1 and the highest levels were found in patients with well controlled hypertension and the lowest in newly diagnosed. All patients diagnosed with hypertension presented negative correlations between PON1 and systolic and diastolic blood pressure. Conclusions Effective treatment of hypertension could result in increased PON1 activity, despite unfavorable homocysteine concentrations in blood. Untreated hypertension might decrease activity of PON.

Metabolomics analysis of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)

AbstractBackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized controlled trial that showed significant benefits on cognition for a 2‐year multidomain lifestyle intervention vs regular health advice in 1260 at‐risk older individuals from the general population. The aim of this study was to investigate the metabolic effects of the intervention and their association with cognitive outcomes.MethodWe acquired metabolomics data of blood plasma on two time points (baseline and 2 years) in a set of 1089 participants (547 intervention and 542 control). A multi‐technology platform consisting of using ultra‐high performance liquid chromatography ‐ mass spectrometry (UHPLC‐MS) and 1H nuclear magnetic resonance spectroscopy (NMR) was used to generate extensive measurement coverage of the metabolome. The data was acquired using both reversed‐phase chromatography (RPC) tailored for the retention and separation of both complex and neutral lipids and hydrophilic interaction liquid chromatography (HILIC) for the retention and separation of small polar metabolites. The UHPLC‐MS untargeted data contains a total of 10,825 metabolomic features, 1244 of them currently annotated. The NMR data contains measurements of both small and macromolecules, including 112 lipoprotein fractions (derived using Bruker lipoprotein subclass analysis: BI‐LISA). Data analysis was conducted using linear mixed models.ResultSeveral baseline metabolite levels had a statistically significant association with cognition. Results will also be presented from ongoing analyses to investigate intervention effects on change in metabolites.ConclusionComplex metabolomics analyses are new in the context of multidomain lifestyle dementia prevention trials. While causality is yet to be investigated further, some of the metabolite classes and pathways observed (e.g. sphingolipids) have been previously implicated in cognitive decline and neurological disorders, suggesting early interpretable leads in the rich dataset at hand.

Anti-SARS-CoV-2 mRNA vaccines as inducers of humoral response against apolipoprotein A-1?

BackgroundCOVID‐19 and some anti‐SARS‐CoV‐2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients’ prognosis in predisposed individuals. Autoantibodies directed against apolipoprotein A‐1 (AAA1 IgG) the major protein fraction of High Density Lipoprotein have been shown to be raised in COVID‐19 and in rheumatoid arthritis (RA) patients and other populations where they have been associated with poorer outcomes. We wanted to assess the impact of anti‐SARS‐CoV‐2 mRNA‐based vaccination on AAA1 autoimmune biomarkers in RA patients.Methods20 healthy controls and 77 RA mRNA‐based vaccinated patients were collected at baseline, 3 weeks after the first vaccination, 2 and 8 weeks after the second vaccination. AAA1 and SARS‐CoV‐2 serologies were measured by immunoassays. Systemic and local symptoms occurring during the vaccination protocol were recorded.ResultsmRNA‐based vaccination induced a significant increase in median AAA1 IgG levels in both healthy controls and RA patients overtime. However, in both populations, these medians trend did not translate into significant increase in AAA1 IgG seropositivity rates despite evolving from 5 to 10% in healthy controls, and from 9 to 12.9% in RA patients. No associations were retrieved between AAA1 IgG and symptoms of any kind during the vaccination protocol.ConclusionsmRNA‐based vaccination seems to induce a light AAA1 IgG response in immunocompetent individuals within 2 months after the last injection. Although we did not observe any warning signs, the formal demonstration of the harmlessness of such biological warrants further studies.

Increased serum amiodarone concentration in hypertriglyceridemic patients: Effects of drug distribution to serum lipoproteins.

Amiodarone and its main metabolite, desethylamiodarone (DEA), are highly distributed to serum lipoproteins such as very‐low‐density lipoprotein (VLDL) and low‐density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone and DEA with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Total serum concentrations of amiodarone and DEA were examined in 116 patients receiving amiodarone for tachyarrhythmias. The concentration‐to‐dose (C/D) ratio of amiodarone positively correlated with the level of serum triglyceride (rs = 0.541, p < 0.001) and was higher in the hypertriglyceridemic state than in normotriglyceridemic state (479 ± 211 vs. 320 ± 161, p < 0.001). No correlation was found between the C/D ratio of DEA and serum triglyceride levels (rs = 0.272), although higher values were observed in the hypertriglyceridemic state (322 ± 125 vs. 285 ± 143, p < 0.001). In the hypertriglyceridemic state, the distribution of amiodarone increased in LDL/VLDL fraction and decreased in high‐density lipoprotein and albumin fractions. The ratio of serum amiodarone to serum DEA, a metabolic ratio of amiodarone, positively correlated with serum triglyceride levels (rs = 0.572, p < 0.001) and was higher in the hypertriglyceridemic state, suggesting that amiodarone metabolism decreased in hyperlipidemia. The results of this study reveal that serum concentrations of amiodarone increase in the hypertriglyceridemic state through the increased lipoprotein‐binding and decreased metabolism of amiodarone.

Abstract 11174: Effect of APOCIII-L Rx on Lipoprotein Size and Particle Numbers Measured by NMR in Patients with Hypertriglyceridemia: Results of the AKCEA-APOCIII-L Rx Trial

Background: APOCIII-L Rx is a hepatocyte-targeted, GalNAc-modified antisense oligonucleotide that decreases plasma levels of apoC-III and triglyceride-rich lipoproteins (TRLs). We examined the effect of APOCIII-L Rx on a variety of lipoprotein fractions measured by nuclear magnetic resonance (NMR) spectroscopy. Methods: The AKCEA-APOCIII-L Rx trial was a dose-ranging study in 114 patients with, or at risk for, ASCVD and fasting serum triglycerides 200-500 mg/dL. Patients (n=114) received AKCEA-APOCIII-L Rx (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6-12 months. Comprehensive NMR LipoProfile ® analysis was performed by LipoScience/LabCorp in frozen EDTA plasma samples collected at baseline and at the primary analysis timepoint (PAT) at 6 months. Results: Results are reported as change from baseline to PAT for the 50 mg every 4 weeks dose versus placebo. APOCIII-L Rx resulted in a significant reduction in total TRL particle (TRLP) concentration by 51% (P&lt;0.0001) with largest reductions in large-size (by 68%, P&lt;0.0001) and medium-size (by 63%, P&lt;0.0001) TRLPs. Total LDL particle (LDLP) concentration was not changed, small LDLP numerically decreased by 39% (P= 0.0713) while medium LDLP increased by 187% (P=0.0119), accompanied by an increase in average LDL size by xx 2% (p=0.0039xx). Total HDL particle (HDLP) concentration increased by 15% (P=0.0006), represented primarily by an increase in small HDL subspecies (particle diameters &lt;8.3 mm) of 32% (P=0.0008). Lower cumulative doses of APOCIII-L Rx generally reflected a dose-dependent relationship in the above parameters. Conclusion: APOCIII-L Rx results in favorable changes in lipoprotein concentration and particle size, primarily manifested by reduction in TRLs, remodeling to larger LDL particles, and increase in small HDLP. These findings suggest an improvement in overall atherogenic risk profile.

Influence of Ketogenic Diet and Nutraceutical Correction in the Complex Treatment of Lower Limbs Lipedema

Currently, the ketogenic diet (KD) is used to treat obesity. A prospective study on the use of KD and nutraceutical correction of the nutritional status of patients with lipedema was carried out. Aim. To study the effect of the ketogenic diet, accompanied by correction of changes in the intestinal microbiome and hepatoprotection,on the reduction of fatty deposits in lipedema and the dynamics of changes in lipid and carbohydrate metabolism hormones. Material and methods. 60 patients with lower limb lipedema of stages I-III were randomized into 2 groups: Group 1 received a lowcalorie diet (LCD), physical exercises in the gym (PE), and physical activity (FA) in the form of daily walking up to 3-5 km/ day. Group 2 received a modified version of the Atkins ketogenic diet, physical exercises in the gym and FA, as well as nutraceutical correction of increased appetite, probiotic intestinal composition, hepatoprotection. The duration of the treatment course was 4 weeks. Anthropometric methods and bioimpedansometry were used to control limb circumferences, waist and thigh. Results and discussion. After treatment, patients in 1st group showed a decrease in body weight, lean and active cell mass, a decrease in musculoskeletal mass, and a decrease in total water due to extracellular water. A decrease in total cholesterol and high density lipoproteins (HDL) fraction, an increase in blood triglyceride fraction was noted. Leptin decreased by 12.73%. Patients of the 2nd group showed a decrease in body weight, fat mass, lean mass, total water and extracellular water. There was a decrease in total cholesterol, triglycerides, transaminases. Leptin decreased by 32.02%, insulin decreased by 9.87%. To prevent the development of fatty hepatosis against the background of the use of KD, patients of the 2nd group received nutraceutical correction: hepatoprotector Gepamin, metaprebiotic Stimbifid-plus, modulating the formation of resident intestinal microbiota. To reduce appetite, the patients of the 2nd group were also prescribed anorexic - an algal product Nativ containing the polysaccharide fucoidan, having a prebiotic effect. Improvement of reparative processes in the liver, suppression of oxidative processes also contributed to the restoration of the sensitivity of insulin receptors, which was confirmed by the normalization of the lipid-carbohydrate spectrum of blood in patients of the 2nd group after the course of the treatment. The insulin decrease in patients of Group 2 indicated not only insulin resistance decrease , but also the lipogenesis decrease and stimulation of lipolysis. Adipose tissue reduction due to lipolysis stimulation was also indicated by a decrease in leptin expression. Conclusion. Thus, a ketogenic diet, accompanied by nutraceutical correction of the intestinal microbiome and hepatoprotection can be effectively used in combination with physical activity in order to reduce body weight, fat mass and edema, as evidenced by a decrease in the expression level of leptin and insulin, correlating with the levels of fat loss and free water.

Whey- and Soy Protein Isolates Added to a Carrot-Tomato Juice Alter Carotenoid Bioavailability in Healthy Adults.

Recent findings suggested that proteins can differentially affect carotenoid bioaccessibility during gastro-intestinal digestion. In this crossover, randomized human trial, we aimed to confirm that proteins, specifically whey- and soy-protein isolates (WPI/SPI) impact postprandial carotenoid bioavailability. Healthy adults (n = 12 males, n = 12 females) were recruited. After 2-week washout periods, 350 g of a tomato-carrot juice mixture was served in the absence/presence of WPI or SPI (50% of the recommended dietary allowance, RDA ≈ 60 g/d). Absorption kinetics of carotenoids and triacylglycerols (TAGs) were evaluated via the triacylglycerol-rich lipoprotein (TRL) fraction response, at timed intervals up to 10 h after test meal intake, on three occasions separated by 1 week. Maximum TRL-carotenoid concentration (Cmax) and corresponding time (Tmax) were also determined. Considering both genders and carotenoids/TAGs combined, the estimated area under the curve (AUC) for WPI increased by 45% vs. the control (p = 0.018), to 92.0 ± 1.7 nmol × h/L and by 57% vs. SPI (p = 0.006). Test meal effect was significant in males (p = 0.036), but not in females (p = 0.189). In males, significant differences were found for phytoene (p = 0.026), phytofluene (p = 0.004), α-carotene (p = 0.034), and β-carotene (p = 0.031). Cmax for total carotenoids (nmol/L ± SD) was positively influenced by WPI (135.4 ± 38.0), while significantly lowered by SPI (89.6 ± 17.3 nmol/L) vs. the control (119.6 ± 30.9, p < 0.001). Tmax did not change. The results suggest that a well-digestible protein could enhance carotenoid bioavailability, whereas the less digestible SPI results in negative effects. This is, to our knowledge, the first study finding effects of proteins on carotenoid absorption in humans.

1H-magnetic resonance spectroscopy lipoprotein profile in patients with chronic heart failure versus matched controls

Introduction and objectivesAdvanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. MethodsThis cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. ResultsThe 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P<.001) and HDL (25.7 vs 27.9μmol/L; P <.001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6μmol/L; P <.001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size. ConclusionsPatients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference.

Distribution of seven ApoC-III glycoforms in plasma, VLDL, IDL, LDL and HDL of healthy subjects

Glycosylation of ApoC-III modulates its function in TG metabolism, with some variants being associated with a more atherogenic lipid profile. These associations have been studied in whole plasma but rarely in individual lipoprotein fractions. In this study, we aimed to measure the relative content of ApoC-III glycoforms in each lipoprotein fraction as a potential biomarker for TG metabolism and cardiovascular risk. Lipoprotein fractions were separated by differential ultracentrifugation of plasma samples from healthy subjects. Relative concentrations of seven ApoC-III variants were measured by MSIA. ApoC-III1, ApoC-III0b and ApoC-III2 were the most abundant glycoforms. There was high interindividual variability in the distribution of glycoforms across the study population but a uniform proportion in all lipoprotein fractions of each given subject. Two ApoC-III variants, ApoC-III0b and ApoC-III1d, negatively correlated with plasma and VLDL triglycerides irrespectively of VLDL size and were associated with increased LDL size when transported in LDL particles. ApoC-III0b also showed a negative correlation with lipoprotein-insulin resistance score. We have been able to measure seven ApoC-III glycoforms in each lipoprotein fraction, setting the basis for future studies exploring their role on cardiovascular risk. Some glycoforms suggest a less proatherogenic role on TG and lipoprotein metabolism. SignificanceApo CIII has an important role on plasma TG metabolism through different mechanisms and it is also involved in type 1 and type 2 Diabetes Mellitus. Different glycosylated forms of Apo CIII exist and they show different roles. For this reason, this protein has gained interest in the las years and the relationship between ApoC-III glycoforms and lipids, lipoproteins and metabolic disorders has been increasingly studied in the last years.Apo CIII glycoforms have been previously analysed in plasma, and the function of the main four glycoforms has been assessed in a variety of cohorts; but in the present study, ApoC-III glycoforms are measured in each lipoprotein fraction, which may be of clinical interest.

Progression of carotid intima-media thickness in patients treated with lipoprotein apheresis: real-world evidence over 12 years

Abstract Background The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular disease (ASCVD) risk reduction. There is limited evidence of long-term effects of lipoprotein apheresis on the CIMT progression. Purpose We hypothesized that regular lipoprotein apheresis over the course of 10 years may slow down progression of CIMT in patients with severe hypercholesterolemia. Methods This case series describes ten Caucasian patients (mean age 60±9 years, 70% female, 80% statin intolerant) with familial hypercholesterolemia and/or hyperlipoproteinemia(a) treated with lipoprotein apheresis at a single academic center between 2005 and 2020. The mean and maximum diastolic CIMT of the distal 1 cm of the far wall of the right and left common carotid arteries was measured by the same, trained sonographer utilizing an automated border-detection algorithm. Results The median pre-treatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/dL (95% confidence interval, 145 to 248), lipoprotein(a), 26 mg/dL (15 to 109; 40% with lipoprotein(a) &amp;gt;60 mg/dL). Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and lipoprotein(a) were 141 mg/dL (IQR, 89 to 152) and 24 mg/dL (IQR, 12 to 119), respectively. The baseline mean CIMT was 850±170μm and maximum CIMT was 1040±220μm across the age range of 46 to 70 years. Over a median duration of 12 years, regular treatment with lipoprotein apheresis resulted in an average reduction in the mean CIMT of −40μm (IQR, −50 to 20) and maximum CIMT −30μm (IQR, −60 to −10). Among tested lipid and lipoprotein fractions in this sample, the follow-up mean CIMT values strongly correlated only with the baseline lipoprotein(a) levels. Median CIMT progression rates were as follows: mean common carotid, −4μm/y (IQR, −9 to 1), mean common carotid, −12μm/3y (IQR, −26 to 4), maximal common carotid, −3μm/y (IQR, −8 to −1). This translated into 70% (7/10) of cases demonstrating composite mean CIMT below their expected chronologic age, gender and race-stratified vascular age. There was a strong direct correlation between the mean CIMT value at the end of the treatment period and the age of treatment initiation. In this cohort of primary and secondary prevention of patients with severe hypercholesterolemia, the overall rate of ASCVD was 37.5 per 1000 person-years while on lipoprotein apheresis. Conclusions Our observation performed in the clinical setting, demonstrated a real-world effectiveness of lipoprotein apheresis. This analysis supports implementation of aggressive lipid-modifying strategies across all ages. Surveillance with CIMT allows for continued monitoring of atherosclerosis progression and increases compliance with the lipid-modifying therapies in the high-risk patients with poor statin tolerance in the clinical setting. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): KUMC

Vascular inflammation and impaired reverse cholesterol transport and lipid metabolism in obese children and adolescents

Background and aimsChildhood obesity is associated to complications such as insulin resistance and dyslipidemia. High density lipoproteins (HDL) constitute the only lipoprotein fraction with ateroprotective properties. The aim of the present study was to analyze inflammatory markers, carbohydrate metabolism, lipid profile and HDL functionality in obese children and adolescents compared to healthy controls. Methods and resultsTwenty obese children and adolescents (Body mass index z score >3.0) (9–15 years old) and 20 age and sex similar controls were included in the study. Triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins (apo) A-I and B, glucose and insulin levels were quantified. Lipid indexes and HOMA-IR were calculated. Cholesterol efflux (CEC), lipoprotein associated phospholipase A2 (Lp-PLA2), lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein, plus paraoxonase and arylesterase (ARE) activities were evaluated. Obese children and adolescents showed significantly higher TG [69 (45–95) vs 96 (76–121); p < 0.05], non-HDL-C [99 ± 34 vs 128 ± 26; p < 0.01], TC/HDL-C [2.8 ± 0.6 vs 4.7 ± 1.5; p < 0.01], TG/HDL-C [1.1 (1.0–1.8) vs 2,2 (1.4–3.2); p < 0.01], and HOMA-IR [1.5 (1.1–1.9) vs. 2.6 (2.0–4.5); p < 0.01] values, plus Lp-PLA2 activity [8.3 ± 1.9 vs 7.1 ± 1.7 umol/ml.h; p < 0,05] in addition to lower HDL-C [57 ± 10 vs 39 ± 9; p < 0.01], apo A-I [143 ± 25 vs 125 ± 19; p < 0.05], and CEC [6.4 (5.1–6.8) vs. 7.8 (5.7–9.5); p < 0.01] plus LCAT [12.6 ± 3.3 vs 18.7 ± 2.6; p < 0.05] and ARE [96 ± 19 vs. 110 ± 19; p < 0.05] activities. Lp-PLA2 activity correlated with LDL-C (r = 0.72,p < 0.01), non-HDL-C (r = 0.76,p < 0.01), and apo B (r = 0.60,p < 0.01). LCAT activity correlated with triglycerides (r = −0.78,p < 0.01), HDL-C (r = 0.64,p < 0.01), and apo A-I (r = 0.62, p < 0.05). ARE activity correlated with HDL-C (r = 0.32,p < 0.05) and apoA-I (r = 0.43,p < 0.01). CEC was negatively associated with BMI z-score (r = −0.36,p < 0.05), and triglycerides (r = −0.28,p < 0.05), and positively with LCAT activity (r = 0.65,p < 0.05). In multivariate analysis, BMI z-score was the only parameter significantly associated to CEC (r2 = 0.43, beta = −0.38, p < 0.05). ConclusionThe obese group showed alterations in carbohydrate and lipid metabolism, which were associated to the presence of vascular specific inflammation and impairment of HDL atheroprotective capacity. These children and adolescents would present qualitative alterations in their lipoproteins which would determine higher risk of suffering premature cardiovascular disease.

Increased Hatchability of Chickens against the Background of the Use of Water-Soluble Antioxidants

The use of antioxidants is an effective means of increasing egg production and hatchability of chickens. The difficulty in application is in the methods of administration of drugs to chickens. Fat-soluble antioxidants are mainly available on the market.&#x0D; Aims: The aim of the study was to study the effectiveness of water-soluble antioxidants on physiological and zootechnical indicators of egg incubation and hatchability of offspring.&#x0D; Methodology: The study was conducted on two groups of laying hens of Ostad, selected by random sampling of one hundred heads per group. For 41 days, the chickens of the experimental group received a basic diet enriched with dihydroetoxychine (DHE) in order to increase the antioxidant status at a dosage of 100 mg/kg of feed. Samples were taken from the axillary vein on the 25th day of application of the supplement (n=5) for physiological and biochemical studies.&#x0D; Results: During the study, it was found that in the experimental group, the concentration of cholesterol in the high-density lipoprotein fraction doubled (P&lt;0.01), and in the low-density lipoprotein fraction decreased by almost 50% (P&lt;0.01) compared to the control. The concentration of malondialdehyde (MDA) in the blood of chickens of the experimental group was 82.00% relative to that in the control, and in the egg yolk – only 37.42%. Egg production of chickens of the experimental group exceeded the control by 7.27%.&#x0D; Conclusion: The totality of the information provided confirms the physiological adequacy for laying hens of the introduction of dihydroethoxychine in the specified dose.

Gemcitabine lipid prodrug nanoparticles: Switching the lipid moiety and changing the fate in the bloodstream

A simple approach to achieve a lipoprotein (LP)–mediated drug delivery is to trigger the spontaneous drug insertion into endogenous lipoproteins in the bloodstream, by means of its chemical modification. Nanoparticles (NPs) made of the squalene–gemcitabine (SQGem) conjugate were found to have a high affinity for plasma lipoproteins while free gemcitabine did not, suggesting a key role of the lipid moiety in this event. Whether the drug conjugation to cholesterol, one of the major lipoprotein-transported lipids, could also promote an analogous interaction was a matter of question. NPs made of the cholesterol–gemcitabine conjugate (CholGem) have been herein thoroughly investigated for their blood distribution profile both in vitro and in vivo. Unexpectedly, contrarily to SQGem, no trace of the CholGem prodrug could be found in the lipoprotein fractions, nor was it interacting with albumin. The investigation of isolated NPs and NPs/LPs physical mixtures provided a further insight into the lack of interaction of CholGem NPs with LPs. Although essential for allowing the self–assembly of the prodrug into nanoparticles, the lipid moiety may not be sufficient to elicit interaction of the conjugated drug with plasma lipoproteins but the whole NP physicochemical features must be carefully considered.

Impact of low-fat and full-fat dairy foods on fasting lipid profile and blood pressure: exploratory endpoints of a randomized controlled trial

Dietary guidelines traditionally recommend low-fat dairy because dairy's high saturated fat content is thought to promote cardiovascular disease (CVD). However, emerging evidence indicates that dairy fat may not negatively impact CVD risk factors when consumed in foods with a complex matrix. The aim was to compare the effects of diets limited in dairy or rich in either low-fat or full-fat dairy on CVD risk factors. In this randomized controlled trial, 72 participants with metabolic syndrome completed a 4-wk run-in period, limiting their dairy intake to ≤3 servings/wk of nonfat milk. Participants were then randomly assigned to 1 of 3 diets, either continuing the limited-dairy diet or switching to a diet containing 3.3 servings/d of either low-fat or full-fat milk, yogurt, and cheese for 12 wk. Exploratory outcome measures included changes in the fasting lipid profile and blood pressure. In the per-protocol analysis (n=66), there was no intervention effect on fasting serum total, LDL, and HDL cholesterol; triglycerides; free fatty acids; or cholesterol content in 38 isolated plasma lipoprotein fractions (P>0.1 for all variables in repeated-measures ANOVA). There was also no intervention effect on diastolic blood pressure, but a significant intervention effect for systolic blood pressure (P=0.048), with a trend for a decrease in the low-fat dairy diet (-1.6±8.6 mm Hg) compared with the limited-dairy diet (+2.5±8.2 mm Hg) in post hoc testing. Intent-to-treat results were consistent for all endpoints, with the exception that systolic blood pressure became nonsignificant (P=0.08). In men and women with metabolic syndrome, a diet rich in full-fat dairy had no effects on fasting lipid profile or blood pressure compared with diets limited in dairy or rich in low-fat dairy. Therefore, dairy fat, when consumed as part of complex whole foods, does not adversely impact these classic CVD risk factors. This trial was registered at clinicaltrials.gov as NCT02663544.

Intensity of CD36 expression by monocyte subpopulations and blood lipid spectrum parameters in patients without established atherosclerotic cardiovascular disease

Introduction. At the current stage of the study of atherosclerosis, it has been established that chronic activation of innate immunity, causing persistent low-intensity sterile inflammation, plays a crucial role at all stages of atherogenesis. Laboratory evaluation of signaling pathways associated with molecular patterns (DAMPs) in atherosclerosis and related to cardiovascular diseases (CVD) may contribute to the discovery of new diagnostic and prognostic markers. Objective: to study the relationship between lipid metabolism parameters and CD36 exposure to circulating monocytes in patientwithout established CVD. Material and methods . The study included 42 patients aged 40–64 years without established atherosclerotic CVD, 19 (45.2 %) men and 23 (54.7 %) women. Dyslipidemia was detected in 95.2 % of patients. The blood serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, glycated hemoglobin, high-sensitivity C-reactive protein (hs-CRP), creatinine were determined with subsequent calculation of glomerular filtration rate. Phenotyping of circulating monocyte subpopulations was performed by flow cytometry on a Navios 6/2 device (Beckman Coulter, USA). Results and discussion . According to the results of correlation analysis, non-HDL cholesterol levels were inversely correlated with absolute ( r = –0.394; p = 0.013) and relative ( r = –0.432; p = 0.006) content of CD14 + CD16 ++ CD36 + TLR2 + monocytes. LDL cholesterol levels were also inversely correlated with the relative content of CD14 + CD16 + CD36 + TLR2 + monocytes ( r = –0.417; p = 0.018). According to correlation analysis, the level of non-HDL cholesterol inversely correlated with the intensity of CD36 expression on classical ( r = –0.650; p &lt; 0.0001), intermediate ( r = –0.323; p = 0.045) and non classical ( r = –0.480; p = 0.002) monocytes. Also, CD36 expression intensity on classical ( r = –0.449; p = 0.004) and non-classical ( r = –0.382; p = 0.016) monocytes was inversely correlated with remnant cholesterol levels. In addition, increased non-HLA cholesterol levels were associated with decreased TLR2 expression on CD14 + CD16 ++ monocytes ( r = –0.381; p = 0.018). It should be noted that a decrease in CD36 expression on intermediate monocytes was also associated with an increase in hs-CRP ( r = –0.657; p = 0.003). Conclusion . In patients without established atherosclerotic CVD, an increase in cholesterol content of atherogenic lipoprotein fractions was associated with a decrease in the number of CD14 + CD16 ++ and CD14 + CD16 + monocytes co-expressing CD36 and TLR2 as well as with a decrease in CD36 expression on classical, intermediate and non-classical monocytes.

Evinacumab for treatment of familial hypercholesterolemia

Introduction Familial hypercholesterolemia (FH) is characterized by lifelong elevation of low-density lipoprotein cholesterol (LDL-C), early onset coronary atherosclerosis and premature death. FH is underdiagnosed and undertreated, but requires aggressive LDL-C-lowering to prevent complications. Current treatment strategies, lifestyle modification and numerous LDL-C-lowering medications, are often insufficient to achieve lipid goals in FH. Areas covered Angiopoietin-like 3 protein (ANGPTL3) is intricately involved in lipid metabolism. Loss-of-function mutations in ANGPTL3 are associated with panhypolipidemia and reduced coronary atherosclerosis. Evinacumab, a fully human monoclonal antibody, inhibits ANGPTL3 and reduces multiple lipoprotein fractions ~50%, including LDL-C. The use of evinacumab within the FH population is described, as well as its regulatory journey to an approved therapeutic. Expert opinion Evinacumab, with its capacity to lower multiple lipoprotein fractions, particularly LDL-C, independently of LDLR function has potential to revolutionize treatment for FH patients. Current FDA-approval is only for homozygous FH (HoFH), arguably the most impactful indication, but use in other lipid disorders is under investigation. Short-term tolerability of evinacumab is very good, with infrequent, mild, and transient adverse events, however, long-term safety data are needed. The high cost and requirement for intravenous administration may limit adoption of evinacumab, but dramatic LDL-C-lowering and need for new therapeutic options for HoFH will drive interest.

Distribution of seven ApoC-III glycoforms in plasma, VLDL, IDL, LDL and HDL of healthy subjects

Background and Aims: ApoC-III is a multifunctional protein involved in atherosclerosis, thrombosis, hepatic steatosis and type 1 and type 2 diabetes mellitus, which makes it a very useful biomarker. ApoC-III activity depends on the lipoprotein in which is transported as well as on the presence of post-translational modifications. These have been studied in whole plasma but rarely evaluated on individual lipoprotein fractions. We aim to prove that up to 7 ApoC-III glycoforms can be measured in each lipoprotein fraction (VLDL, IDL, LDL, HDL) in subjects with low apoC-III concentrations.

Hypocholesterolemic Effect of Blackcurrant (Ribes nigrum) Extract in Healthy Female Subjects: A Pilot Study.

Blackcurrant extract (BCE) ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can prevent lipid abnormalities in healthy individuals. Lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined the effects of BCE administered for 29 days on serum lipids in young healthy women. Blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in the serum were separated using a gel-permeation high-performance liquid chromatography method to measure the triacylglycerol and cholesterol levels in lipoproteins. There were no effects on lipids on day 4 of BCE intake, but the total cholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL) cholesterol, small VLDL cholesterol, and large low-density lipoprotein cholesterol were significantly decreased. These results suggest that the daily intake of BCE has a hypocholesterolemic effect in healthy women, and that it is effective in preventing atherosclerosis.