High Concentrations Of Low Density Lipoprotein Research Articles

Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism. We previously induced Dox resistance in TNBC cell models, characterizing a variant denominated as variant B cells. Our results suggest that LDL internalization in parental and chemoresistant variant B cells is associated with increased cell proliferation, migration, invasion, and spheroid growth. We identified the role of eIF4F translation initiation factor and the down-regulation of tumor suppressor gene PDCD4, an inhibitor of eIF4A, in chemoresistant variant B cells. In addition, the exomes secreted by variant B cells were characterized by the protein content, electronic microscopy, and cell internalization assays. Critically, exosomes purified from LDL-treated variant B cell promoted cell proliferation, migration, and an increment in lactate concentration. Our results suggest that an autocrine phenomenon induced by exosomes in chemoresistant cells may induce modifications on signaling mechanisms of the p53/Mdm2 axis and activation of p70 ribosomal protein kinase S6. Moreover, the specific down-regulated profile of chaperones Hsp90 and Hsp70 secretion inside the exosomes of the chemoresistant variant could be associated with this phenomenon. Therefore, autocrine activation mediated by exosomes and the effect of LDL internalization may influence changes in exosome chaperone content and modulate proliferative signaling pathways, increasing the aggressiveness of MDA-MB-231 chemoresistant cells.

Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study

Background and aimsThe lipid profile is consistently associated with coronary artery disease (CAD) and ischemic stroke (IS). However, the lipoprotein subfractions have not been deeply explored in stroke subtypes, especially in IS outcome. MethodsWe performed two-sample Mendelian randomization (MR) analysis using 92 lipid traits measured by nuclear magnetic resonance in 115,000 subjects from the UK Biobank. Data for genetic associations with IS, its subtypes, and long-term outcome (LTO) were obtained from three cohorts of European ancestry: GIGASTROKE (73,652 cases, 1,234,808 controls), GODS (n = 1791) and GISCOME (n = 6165). Results obtained using CARDIoGRAMPlusC4D were used to identify differences with CAD. ResultsGenetically determined low concentration of medium high-density lipoprotein (HDL) particles (odds ratio (OR) = 0.92, 95% CI 0.88–0.96; p = 3.6 × 10−4) and its cholesterol content (OR = 0.92, 95% CI 0.88–0.96; p = 1.9 × 10−4) showed causal associations with an increased risk of stroke. Genetic predisposition to high apolipoprotein (apo)B to apoA-I ratio was causally associated with an increased risk of IS (OR = 1.12, 95% CI 1.06–1.18, p = 1.1 × 10−4), and a highly suggestive association was found between non-esterified cholesterol in low-density lipoprotein (LDL) and increased risk of atherothrombotic stroke (LAS) (OR = 1.35, 95% CI 1.10–1.66; p = 4.0 × 10−3). Low cholesterol in small and medium LDL was suggestively associated with poor LTO. ConclusionsOur results support that low medium HDL concentration was causally associated with an increased stroke risk, while high levels of non-esterified cholesterol in LDL were suggestively associated with an increased risk of LAS and with a better LTO.

Lipids, lipoproteins, and apolipoproteins during the first year of life: a prospective cohort study

Abstract Background/Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and treatment of well-established lifestyle risk factors are cornerstones in CVD prevention. An atherogenic lipid profile with high concentrations of low-density lipoprotein (LDL) cholesterol and other apolipoprotein B containing lipoproteins is a driving force in the pathogenesis of atherosclerotic CVD (ASCVD). The lifelong atherosclerotic process is proportional to concentrations of apolipoprotein B-containing lipoproteins, hence risk of developing ASCVD is cumulative over time. The higher the baseline concentrations, the sooner the threshold for increased risk of ASCVD will be reached. It is therefore crucial to implement changes as early as possible and prevent risk factors in occurring – so-called primordial prevention. Childhood has been described as a "window of opportunity" for preventing risk factors in occurring and thus avoiding ASCVD. Whether concentrations of atherogenic lipoproteins at birth can predict future concentrations in early childhood and thus may indicate increased risk of dyslipidemia later in life remains unknown. Purpose The aim of the present study was to investigate atherogenic lipid traits during the first year of life, to identify influential factors for lipid concentrations, and to determine whether concentrations at birth can predict future lipid concentrations in early childhood. Methods For this purpose, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n=444), at two months (n=363), and at 14-16 months (n=158). Lipid traits were determined in all samples. Results Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B increased during the first year of life. Girls had higher concentrations at birth and at two months compared with boys. Children born preterm had higher cord blood concentrations than children born at term. A linear mixed model showed that high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth predicted high concentrations at two months and at 14-16 months. Multivariable adjusted odds ratios (95% CI) for having high concentrations at two months when children had high concentrations at birth were 1.95 (1.01-3.79) for LDL cholesterol, 1.36 (0.69-2.67) for non-HDL cholesterol and 1.90 (1.02-3.53) for apolipoprotein B. Conclusion The lipid profile change during the first year of life and sex and gestational age influence concentrations. Children with high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth had higher levels at two and at 14-16 months. Concentrations at birth may thus be used to identify children at risk of dyslipidemia in later life.

Computational modeling of low-density lipoprotein accumulation at the carotid artery bifurcation after stenting.

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS.

Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association

Abstractvon Willebrand factor (VWF) mediates primary hemostasis and thrombosis in response to hydrodynamic forces. We previously showed that high shear promoted self-association of VWF into hyperadhesive strands, which can be attenuated by high-density lipoprotein (HDL) and apolipoprotein A-I. In this study, we show that low-density lipoprotein (LDL) binds VWF under shear and enhances self-association. Vortexing VWF in tubes resulted in its loss from the solution and deposition onto tube surfaces, which was prevented by HDL. At a stabilizing HDL concentration of 1.2 mg/mL, increasing concentrations of LDL progressively increased VWF loss, the effect correlating with the LDL-to-HDL ratio and not the absolute concentration of the lipoproteins. Similarly, HDL diminished deposition of VWF in a post-in-channel microfluidic device, whereas LDL increased both the rate and extent of strand deposition, with both purified VWF and plasma. Hypercholesterolemic human plasma also displayed accelerated VWF accumulation in the microfluidic device. The initial rate of accumulation correlated linearly with the LDL-to-HDL ratio. In Adamts13−/− and Adamts13−/−LDLR−/− mice, high LDL levels enhanced VWF and platelet adhesion to the myocardial microvasculature, reducing cardiac perfusion, impairing systolic function, and producing early signs of cardiomyopathy. In wild-type mice, high plasma LDL concentrations also increased the size and persistence of VWF-platelet thrombi in ionophore-treated mesenteric microvessels, exceeding the accumulation seen in similarly treated ADAMTS13-deficient mice that did not receive LDL infusion. We propose that targeting the interaction of VWF with itself and with LDL may improve the course of thrombotic microangiopathies, atherosclerosis, and other disorders with defective microvascular circulation.

Effect of Bajakah Tea Extract (Spatholobus littoralis Hassk) on High Density Lipoprotein, Triglyceride and Total Cholesterol Levels in Male Wistar Rats

Hyperlipidemia is the high concentrations of low-density lipoprotein, cholesterol, and triglycerides in the blood. Furthermore, hyperlipidemia has a risk factor for cardiovascular complications through atherosclerosis that triggers coronary heart disease (CHD). Spatholobus littoralis Hassk known as Bajakah tea is a plant with high antioxidant content and acts as an HMG-CoA reductase inhibitor to suppress lipid metabolism disorders, increase HDL levels, and reduce triglycerides and total cholesterol. Experimental and posttest control group design methods were used to obtain 24 male Wistar rats. Furthermore, the experimental animals were randomly divided into 4 groups, namely K1 (normal rats), K2 (hyperlipidemia rats), K3 (hyperlipidemic rats + pirated tea extract dose 9 mg/200gramBW/day), and K4 (hyperlipidemic rats + simvastatin dose 0.18 mg/200 gBW/day). The study was conducted at the Center for Food and Nutrition Studies Laboratory, Gajah Mada University, Yogyakarta. Data levels of HDL, triglycerides, and total cholesterol were analyzed using the One Way Anova test and LSD post hoc to determine between groups. The results showed that an increase in triglyceride and total cholesterol and a decrease in HDL levels in the K2 group compared to the K1. Triglyceride and total cholesterol decreased in groups K3 and K4 compared to K2, and HDL levels increased in groups K3 and K4 compared to K2. Meanwhile, the results of the analysis obtained p value <0.05. This study concluded that the administration of Bajakah tea extract at a dose of 9 mg/200gram BW/day for 14 days increase HDL, reduce triglyceride and total cholesterol levels (p<0,05).

Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients.

Introduction Cardiovascular diseases are the leading cause of death worldwide. The combination of statins and cholesterol-absorption inhibitors promotes the decrease in risk factors, such as high concentrations of LDL (low-density lipoproteins). The aim of the study was to evaluate changes in the lipid profile and the effect on therapeutic goals, as well as the safety of dyslipidemia patients treated with Rosuvastatin/Ezetimibe (Trezete®). Materials and Methods A real-world evidence study was conducted with retrospective data collection through a review of clinical records from dyslipidemia patients treated with Trezete® in routine medical practice. Clinical records included results of biochemical markers before treatment and at least one follow up between weeks 8 and 16. Results The study included 103 patients' clinical records (55.4% men) with a mean age of 56.0 ± 13.0 years. More than 57% of the patients had mixed dyslipidemia and a median disease progression of 3.1 (IQR, 1.5; 9.1) years. Regarding LDL concentrations, 72.8% of the patients achieved therapeutic goals according to cardiovascular risk (CVR), which was statistically significant. Similarly, 94.1% achieved goals for total cholesterol (<200 mg/dL) and 56.0% for triglycerides (<150 mg/dL), a p value <0.001. No cardiovascular events were observed. Conclusion Trezete® shows an important clinical impact on CVR-related target markers during the treatment of dyslipidemia patients. It is relevant to mention that a significant percentage of patients achieved therapeutic goals during the first months of treatment. Fixed-dose combination therapy has shown to be as safe as monotherapy treatment. ClinicalTrials.gov Identifier: NCT04862962.

Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia.

High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

Blood Lead and High-Density Lipoprotein Concentrations in Relation to Human Blood Pressure: A Cross Sectional Study.

BackgroundWhile the relationship between blood pressure and blood lead has been studied more extensively, the effect of high-density lipoprotein (HDL) concentration on this relationship remains uncertain. Therefore, this study aimed to determine the effect of HDL concentration on the relationship between blood lead and blood pressure.MethodsThe research used cross-sectional data from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES), which included 16,451 participants aged 20–60 years. Multivariable linear regression was used to evaluate the correlation among blood lead, systolic blood pressure (SBP), and diastolic blood pressure (DBP). HDL concentration was determined by low HDL concentration (≤ 49 mg/dl) and high HDL concentration (>49 mg/dl) stratified. The effect of HDL concentration was assessed by an interaction test between blood lead and SBP in multivariable linear regression.ResultsIn this cross-sectional research, we identified a positive correlation between blood lead and SBP, but not DBP. The relationship between blood lead and SBP was different in the group with low and high HDL concentrations (β: 0.21 95% Cl:−0.05-0.46 vs. β:0.47 95% Cl: 0.15-0.79). In addition, high HDL significantly altered the positive correlation between blood lead and SBP (P-value of interaction < 0.001).ConclusionThe study suggests an interaction between HDL and blood lead in elevating SBP, which may have important clinical implications.

Interactive effects of the low-carbohydrate diet score and genetic risk score on Hypo-HDL-cholesterolemia among Korean adults: A cross-sectional analysis from the Ansan and Ansung Study of the Korean Genome and Epidemiology Study.

This cross‐sectional study investigated the interaction between the genetic risk score (GRS) and abnormal high‐density lipoprotein (HDL) cholesterol lipid levels, which are modified by low‐carbohydrate diets (LCDs) and their effects on the prevalence of hypo‐HDL‐cholesterolemia (hypo‐HDL‐C) in Korean adults. Baseline data were obtained from the Ansan and Ansung study of the Korean Genome and Epidemiology Study (KoGES), conducted from 2001 to 2002, that targeted 8,314 Korean adults aged 40–69 years, including old men (47.6%) and women (52.4%), and whole genomic single nucleotide polymorphism (SNP) genotyping was performed. We identified 18 SNPs significantly associated with hypo‐HDL‐C in the proximity of several genes, including LPL, APOA5, LIPC, and CETP, and calculated the GRS. The low‐carbohydrate diet score (LCDS) was calculated on the basis of energy intake information from food frequency questionnaires. Furthermore, we performed multivariable‐adjusted logistic modeling to examine the odds ratio (OR) for hypo‐HDL‐C across tertiles of LCDS and GRS, adjusted for several covariates. Among participants in the highest GRS tertile, those in the highest tertile of the LCDS had a significantly lower risk of hypo‐HDL‐C (OR: 0.759, 95% CI (confidence interval): 0.625–0.923) than those in the lowest tertile of the LCDS. In the joint effect model, the group with the lowest GRS and highest LCDS was found to have the lowest risk of hypo‐HDL‐C prevalence. This study suggests that individuals with a high genetic risk for low HDL concentrations may have a beneficial effect on a lower intake of carbohydrates.

Elevated Plasma Concentrations of Vitamin D-Binding Protein Are Associated with Lower High-Density Lipoprotein and Higher Fat Mass Index in Overweight and Obese Women.

(1) Background: Observational studies have established that vitamin D-binding protein (DBP) and 25-hydroxyvitamin D3 (25(OH)D) concentrations are the major factors affecting the bioavailability of 25(OH)D. It has also been shown that poor 25(OH)D bioavailability elevates the risk of obesity and its related cardio-metabolic disorders. However, the relationship between 25(OH)D and DBP concentrations with cardio-metabolic risk factors in overweight and obese cohorts has not been established. Consequently, we evaluated the association between DBP and 25(OH)D concentrations with lipid profile, blood pressure (BP), and body composition in overweight and obese women. (2) Methods: In this cross-sectional study of 236 overweight and obese women, DBP and 25(OH)D concentrations were measured using an enzyme-linked immunosorbent assay. Body composition was assessed via bioelectrical impedance analysis. Lipid profile and BP were assessed by an auto-analyzer and digital BP monitor, respectively. The associations were examined by multivariate logistic regression. (3) Results: The indicated showed an inverse relationship between DBP and high-density lipoprotein (HDL) (p = 0.010) concentrations (where individuals with higher DBP had lower HDL) which, after adjusting for possible cofounders, remained significant (p = 0.006). Moreover, DBP concentration was positively associated with fat mass index (FMI) after adjustment (p = 0.022). No significant relationships were observed among 25(OH)D and target variables. (4) Conclusions: In conclusion, lower concentrations of HDL and higher values of FMI are associated with higher concentrations of DBP in overweight and obese women. These findings present novel awareness regarding the association of DBP with some metabolic and body composition variables in overweight and obese women. However, a two-way causal relationship between DBP and target variables should be considered.

Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women: Results From the ENIGI Study.

ContextCyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent.ObjectiveTo assess the lowest effective dose of CPA in trans women to prevent side effects.MethodsThis longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n = 882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of hormone therapy.ResultsUsing estrogens only (without CPA) led to testosterone concentrations of 5.5 nmol/L (standard error of the mean [SEM] 0.3). All doses of CPA resulted in testosterone concentrations below the predefined threshold of suppression of 2 nmol/L (10 mg, 0.9 nmol/L, SEM 0.7; 25 mg, 0.9 nmol/L, SEM 0.1; 50mg, 1.1 nmol/L, SEM 0.1; 100 mg, 0.9 nmol/L, SEM 0.7). Higher prolactin and lower high-density lipoprotein concentrations were observed with increasing doses of CPA. No differences in liver enzyme concentrations were found between the doses.ConclusionCompared with higher doses of CPA, a daily dose of 10 mg is equally effective in lowering testosterone concentrations in trans women, while showing fewer side effects.

Protection against Glucolipotoxicity by High Density Lipoprotein in Human PANC-1 Hybrid 1.1B4 Pancreatic Beta Cells: The Role of microRNA.

Simple SummaryLoss of the cells which secrete insulin, the hormone which controls blood sugar levels, can occur due to the damaging effects of high levels of sugar and fat in the bloodstream, and is a key factor which triggers type 2 diabetes. Protection against this damage is provided by one of the fat and protein complexes which carry the ‘good’ cholesterol in the bloodstream, a complex which is called high-density lipoprotein. This study looks at the changes in the expression of small pieces of RNA, called microRNA, triggered in insulin-secreting cells by treatment with high density lipoprotein. These small RNA sequences can help to regulate the expression of genes which can contribute to the protective effect of high-density lipoproteins. Delivery of one of these sequences was able to modulate gene expression in cells, but could not provide enough protection against the damaging effects of high sugar and fat. We conclude that the complex changes in numerous microRNA sequences caused by high density lipoproteins cannot be replicated by a single sequence, suggesting that networks of regulatory microRNA sequences are more important than single sequences. The results will inform drug discovery strategies which focus on high density lipoprotein and microRNA. High-density lipoproteins provide protection against the damaging effects of glucolipotoxicity in beta cells, a factor which sustains insulin secretion and staves off onset of type 2 diabetes mellitus. This study examines epigenetic changes in small non-coding microRNA sequences induced by high density lipoproteins in a human hybrid beta cell model, and tests the impact of delivery of a single sequence in protecting against glucolipotoxicity. Human PANC-1.1B4 cells were used to establish Bmax and Kd for [3H]cholesterol efflux to high density lipoprotein, and minimum concentrations required to protect cell viability and reduce apoptosis to 30mM glucose and 0.25 mM palmitic acid. Microchip array identified the microRNA signature associated with high density lipoprotein treatment, and one sequence, hsa-miR-21-5p, modulated via delivery of a mimic and inhibitor. The results confirm that low concentrations of high-density lipoprotein can protect against glucolipotoxicity, and report the global microRNA profile associated with this lipoprotein; delivery of miR-21-5p mimic altered gene targets, similar to high density lipoprotein, but could not provide sufficient protection against glucolipotoxicity. We conclude that the complex profile of microRNA changes due to HDL treatment may be difficult to replicate using a single microRNA, findings which may inform current drug strategies focused on this approach.

Low HDL concentration in rs2048327-G carriers can predispose men to develop coronary heart disease: Tehran Cardiometabolic genetic study (TCGS).

Recent genome-wide association studies (GWAS) highlighted the importance of genetic variations on SLC22A3 and MIA3 genes in developing coronary heart disease (CHD) among different ethnicities. However, the influence of these variations is not recognized within the Iranian population. Hence, in the present study, we aim to investigate two key single nucleotide polymorphisms (SNPs) on CHD incidence in this population. For this purpose, from Tehran Cardiometabolic Genetic Study (TCGS), 453 individuals with CHD were selected as a case and 453 individuals as a control that matched their age and gender. After quality control of two selected SNPs, rs2048327 (SLC22A3) and rs17465637 (MIA3), we used genotyps resulted from chip-typing technology and conducted the logistic regression analysis adjusted for non-genetic risk factors to detect the possible association of these SNPs with the CHD development. Our findings demonstrated the rs2048327-G and rs17465637-C can significantly increase the risk of CHD development about two times in only males and females, respectively. Interestingly, in the male carriers of the risk allele (G) of rs2048327, the low high-density lipoprotein (HDL) level can significantly predispose them to develop coronary heart disease in the future. According to our results, paying more attention to gender and genetic markers can help more efficient coronary heart disease screening and diagnosis.

The role of proprotein convertase subtilisin/kexin type-9 concentration and paraoxonase 1 activities in the blood of women with polycystic ovary syndrome

This study aimed to evaluate the concentration of proprotein convertase subtilisin/kexin type-9 (PCSK9) and the activities of paraoxonase 1 in women with and without polycystic ovary syndrome (PCOS). We found significant higher PCSK9, whereas lower high-density lipoprotein concentration in the serum of women with PCOS when compared to the group without PCOS. Also paraoxonase 1 activities were significantly different between women with PCOS than without PCOS. In addition, the women with PCOS and insulin resistance had higher concentrations of PCSK9 than women with PCOS and insulin sensitivity. Higher PCSK9 concentration in the group with PCOS could be also associated with hormones concentrations.Changes in paraoxonase 1 activities and lipid profile parameters as well as higher concentration of PCSK9 in the group of women with PCOS could be associated with metabolism disorders, but due to the small clinical sample size, the study should be continued.

Effects of methionine as free amino acid and dipeptide on productive efficiency and meat quality of broilers under acute and chronic heat stress

Context Methionine in the form of free amino acid has been widely studied in broilers challenged by heat stress (HS). However, the effects of methionine dipeptide in broilers subjected to HS are not known. Aims To evaluate the effects of methionine as free amino acid and dipeptide on the performance, oxidative status, plasma parameters and meat quality of broilers subjected to acute and chronic HS. Methods Broilers were evaluated at the following three experimental periods: 24 h of evaluation (21–22 days of age); 10 days of evaluation (22–32 days of age); and 20 days of evaluation (22–42 days of age). Broilers were divided into two groups; one group was raised in thermal comfort, and the other group was raised in continuous HS of 30°C. In both groups, animals received a diet without methionine supplementation (MD), with supplementation of methionine as free amino acid (dl-M), and with supplementation of methionine as dipeptide (dl-MM). Key results HS reduced body weight gain after 10 and 20 days of evaluation. Broilers under HS condition fed the MD diet had the highest concentrations of thiobarbituric acid reactive substances (TBARS) at 22 days of age and carbonylated proteins (CP) at 32 days of age. At 42 days of age, broilers fed the MD diet had higher concentrations of TBARS and CP. At 32 days of age, broilers under HS had lower high-density lipoprotein and higher low-density lipoprotein concentrations. In breast meat, broilers in thermal comfort fed the dl-M or dl-MM diets had a lower cooking loss. Broilers in HS fed the dl-M diet had the lowest cooking loss. HS reduced the pH of the meat of legs. Conclusions The acute and chronic HS affect the broiler performance in different ways. Methionine supplementation contributes to reduce the effects of HS. There were no notable differences between the supplementation of dl-M or dl-MM. Implications Productivity and the quality of the chicken meat are the most important attributes of the production. The ambient temperature can influence these parameters. The methionine in its most varied forms, due to its direct and indirect antioxidant function, has been shown to be an effective source of protection for the animal in adverse conditions such as during HS.

The Allergenic Role of the Drug Excipient in a Case of Allergy in Pcsk-9 Inhibitor

Hyperlipidemia is a well-established risk factor for the development of cardiovascular disease (CVD) [1]. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are novel drugs in use against hyperlipidemia [2]. The gene for this enzyme is encoded by the PCSK9 gene that is located on chromosome 1. This gene contains one of 27 loci associated with increased risk of coronary artery disease [3, 4]. PCSK-9 is expressed in many tissues and it has the ability to bind to low-density lipoprotein receptor (LDL-R) and to reduce its number on the extracellular side of cell membranes. This results in a decreased ability of the cells to uptake low-density lipoprotein (LDL) and in this way, in a higher concentration of LDL in blood circulation [5]. Therefore, blocking PCSK-9 can lower blood LDL concentrations thus having an important medical importance [6]. We present a case of allergy on Alirocumab only, one of PCSK-9 inhibitors.

PAH exposure is associated with enhanced risk for pediatric dyslipidemia through serum SOD reduction

BackgroundExposure to polycyclic aromatic hydrocarbons (PAHs) is linked to abnormal lipid metabolism, but evidence regarding PAHs as risk factors for dyslipidemia is lacking. ObjectiveTo investigate the respective role and interaction of PAH exposure and antioxidant consumption in the risk for pediatric dyslipidemia. MethodsWe measured the concentrations of serum lipids, superoxide dismutase (SOD) and urinary hydroxylated PAHs (OH-PAHs) in 403 children, of which 203 were from an e-waste-exposed area (Guiyu) and 200 were from a reference area (Haojiang). Biological interactions were calculated by additive models. ResultsGuiyu children had higher serum triglyceride concentration and dyslipidemia incidence, and lower serum concentration of high-density lipoprotein (HDL) than Haojiang children. Elevated OH-PAH concentration, and concomitant SOD reduction, were both associated with lower HDL concentration and higher hypo-HDL risk (∑3OH-Phes: B for lgHDL = −0.048, P < 0.01; OR for hypo-HDL = 3.708, 95% CI: 1.200, 11.453; SOD: BT3 for lgHDL = 0.061, P < 0.01; ORT3 for hypo-HDL = 0.168, 95% CI: 0.030, 0.941; all were adjusted for confounders). Biological interaction between phenanthrol exposure and SOD reduction was linked to dyslipidemia risk (RERI = 2.783, AP = 0.498, S = 2.537). Children with both risk factors (higher ∑3OH-Phes and lower SOD) had 5.594-times (95% CI: 1.119, 27.958) the dyslipidemia risk than children with neither risk factors (lower ∑3OH-Phes and higher SOD). ConclusionHigh PAH exposure combined with SOD reduction is recommended for predicting elevated risk for pediatric dyslipidemia. Risk assessment of PAH-related dyslipidemia should take antioxidant concentration into consideration.

The Effects of Linoleic Acid Consumption on Lipid Risk Markers for Cardiovascular Disease in Healthy Individuals: A Review of Human Intervention Trials.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Risk factors for developing this disease include high serum concentrations of total cholesterol, triglycerides, low-density lipoproteins, very-low density lipoproteins, and low concentrations of high-density lipoproteins. One proposed dietary strategy for decreasing risk factors involves replacing a portion of dietary saturated fatty acids with mono- and polyunsaturated fatty acids (PUFAs). The essential omega-6 PUFA, linoleic acid (LA), is suggested to decrease the risk for CVD by affecting these lipid risk markers. Reviewing human intervention trials will provide further evidence of the effects of LA consumption on risk factors for CVD. PubMed was used to search for peer-reviewed articles. The purpose of this review was: (1) To summarize human intervention trials that studied the effects of LA consumption on lipid risk markers for CVD in healthy individuals, (2) to provide mechanistic details, and (3) to provide recommendations regarding the consumption of LA to decrease the lipid risk markers for CVD. The results from this review provided evidence that LA consumption decreases CVD lipid risk markers in healthy individuals.

Assessing the Prevalence of Dyslipidemia in Apparently Healthy Urban Obese Adults Residing in South Delhi, India

The present research study was conducted to assess the prevalence and pattern of dyslipidemia in apparently healthy urban obese adults residing in South Delhi. Dyslipidemia and obesity are two prominent contributing risk factors for cardiovascular disease. This cross-sectional study was conducted among 150 apparently healthy obese adults with a body mass index of ≥25 kg/m2. Data regarding the socio-demographic characteristics as well as anthropometric parameters were collected. To evaluate serum lipid levels fasting blood samples were collected by trained technicians and analysis was carried out in a certified laboratory. Dyslipidemia was defined as the presence of hypercholesterolemia, high levels of low-density lipoprotein (LDL) cholesterol, and /or lower concentration of high-density lipoprotein (HDL), present alone or in combination. The overall prevalence of dyslipidemia was noted to be 78%. The prevalence was observed to be much higher in the obese female subjects (81.43%) than the obese males (75%). Mean triglycerides levels were significantly higher in the obese men than females while, HDL–C levels were higher in the female subjects (p<0.05). Further, it was seen that low concentration of HDL was the most prevailing deranged lipid parameter (52.67%) followed by elevated triglycerides levels (49.33%) and elevated LDL levels (39.33%) in these obese adults. The study thus highlights the importance of regular and timely screening for apparently healthy populations. Advocating suitable and timely medical and dietary interventions can help in both monitoring and avoiding further health-related complications.