Low Density Lipoprotein Composition Research Articles

Distinct Microbial Taxa Are Associated with LDL-Cholesterol Reduction after 12 Weeks of Lactobacillus plantarum Intake in Mild Hypercholesterolemia: Results of a Randomized Controlled Study.

Probiotic microbes such as Lactobacillus may reduce serum total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol. The objective of this study was to assess the effect of Lactobacillus plantarum strains CECT7527, CECT7528, and CECT7529 (LP) on the serum lipids, cardiovascular parameters, and fecal gut microbiota composition in patients with mild hypercholesterolemia. A randomized, double-blinded, placebo-controlled clinical trial with 86 healthy adult participants with untreated elevated LDL cholesterol ≥ 160mg/dl was conducted. Participants were randomly allocated to either placebo or LP (1.2 × 109CFU/d) for 12weeks. LDL, HDL, TC, and triglycerides (TG), cardiovascular parameters (blood pressure, arterial stiffness), and fecal gut microbiota composition (16S rRNA gene sequencing) were assessed at baseline and after 12weeks. Both groups were comparable regarding age, sex, and LDL-C at baseline. LDL-C decreased (mean decrease - 6.6mg/dl ± - 14.0mg/dl, Ptime*group = 0.006) in the LP group but not in the placebo group. No effects were observed on HDL, TG, or cardiovascular parameters or overall gut microbiota composition. Responders to LP intervention (> 5% LDL-C reduction) were characterized by higher BMI, pronounced TC reduction, higher abundance of fecal Roseburia, and lower abundance of Oscillibacter. In conclusion, 12weeks of L. plantarum intake moderately reduced LDL-C and TC as compared to placebo. LDL-C-lowering efficacy of L. plantarum strains may potentially be dependent on individual difference in the gut microbiota. Trial registration: DRKS00020384, dated 07/01/2020.

The human liver lipidome is significantly related to the lipid composition and aggregation susceptibility of low-density lipoprotein (LDL) particles

Background and aimsThe susceptibility of low-density lipoprotein (LDL) to aggregation predicts atherosclerotic cardiovascular disease. However, causes of interindividual variation in LDL lipid composition and aggregation susceptibility remain unclear. We examined whether the lipid composition and aggregation susceptibility of LDL reflect the lipid composition of the human liver. MethodsLiver biopsies and blood samples for isolation of LDL particles were obtained from 40 obese subjects (BMI 45.9 ± 6.1 kg/m2, age 43 ± 8 years). LDL was isolated using sequential ultracentrifugation and lipidomic analyses of liver and LDL samples were determined using ultra-high performance liquid chromatography–mass spectrometry. LDL aggregation susceptibility ex vivo was analyzed by inducing aggregation by human recombinant secretory sphingomyelinase and following aggregate formation. ResultsThe composition (acyl carbon number and double bond count) of hepatic triglycerides, phosphatidylcholines, and sphingomyelins (SMs) was closely associated with that of LDL particles. Hepatic dihydroceramides and ceramides were positively correlated with concentrations of the corresponding SM species in LDL as well with LDL aggregation. These relationships remained statistically significant after adjustment for age, sex, and body mass index. ConclusionsLipid composition of LDL reflects that of the human liver in obese patients. Changes in hepatic sphingolipid metabolism may contribute to interindividual variation of LDL lipid composition and susceptibility to aggregation.

Quality matters: low-density lipoprotein electronegativity but not quantity determines mortality risk in acute coronary syndromes

Abstract Background Changes in the protein composition of low-density lipoprotein (LDL) particles induce a shift in their electronegativity, a phenomenon implicated in both pro-inflammatory and pro-atherogenic signalling (1). While high levels of LDL foster the build-up of atherosclerotic plaques, and as such the susceptibility for the development of acute coronary syndromes (ACS), LDL levels assessed at the time of presentation fail to associate with fatal events following the index event (2). Experimental data suggest that altered LDL electronegativity exerts functional effects on both the myocardium and vasculature (1,3). Purpose We aimed to study the association between LDL electronegativity, assessed at the time of acute presentation, and all-cause mortality following the index ACS. Methods We designed a case-cohort study in 2'619 ACS patients prospectively recruited in the investigator-driven, multicentre SPUM-ACS study (ClinicalTrials.gov Identifier: NCT01000701). Plasma LDL levels were quantified at baseline and LDL was chromatographically resolved into 5 subfractions (L1-L5), with the L1/L5 ratio serving as a proxy for overall LDL electronegativity. By employing least-squares ordinary regression models determinants of plasma L1, L5, and the L1/5 ratio were studied, and the association with mortality of both LDL levels and its electronegativity were estimated using weighted Cox regression models. Results Cases and controls showed similar lipid profiles, but distinct LDL electronegativity, demonstrated by an increase in the L1/L5 ratio in cases vs. controls (P<0.05; Fig. 1). The highest-ranked determinants of the L1/L5 ratio were total cholesterol, LDL, high-density lipoprotein, age and triglycerides. Higher L1/L5 ratios were associated with increased risk all-cause and cardiovascular death at both 30-day (adjusted [adj.] hazard ratio [HR], 2.35, 95% confidence interval [CI], 1.81–3.03, and 2.37, 95% CI, 1.83–3.07, per standard-deviation [SD] increase) and 1-year intervals (adj. HR, 1.88, 95% CI 1.43–2.46, and 1.81, 95% CI 1.36–2.42 per SD increase). In contrast, LDL levels were not associated with these outcomes, neither at 30-day (adj. HR, 1.20, 95% CI, 0.64–2.24, and 1.20, 95% CI, 0.64–2.56 per SD increase) nor 1-year intervals (adj. HR, 1.35, 95% CI, 0.69–2.63, and 1.25, 95% CI 0.56–2.78 per SD increase). These associations were independent of age, sex, cardiometabolic risk factors and baseline risk, as assessed by the updated GRACE score. When compared with established risk factors (hsTnT levels, BMI, Killip class, eGFR, LDL levels), the L1/L5 ratio superseded several risk factors as an independent predictor for fatal events following ACS (Fig. 2). Conclusions In contemporary patients with ACS, LDL electronegativity independently predicts fatal events after the acute event, while LDL levels do not. Our results suggest that LDL quality rather than quantity provides predictive utility for premature death within 1 year after the index ACS. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science FoundationSwiss Heart FoundationTheodor-Ida Herzog StiftungFoundation for Cardiovascular Research – Zurich Heart House

Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia.

Maternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase subtilisin/kexin type 9 (PCSK9) levels (a protein that regulate the availability of LDL receptor in the cells surface), as well as the composition and function of LDL, are modulated in MSPH women. This study included 122 pregnant women. Maternal total cholesterol (TC), LDL, triglycerides and PCSK9 increased from first (T1) to third trimester (T3) in MPH women. At T3, maternal TC, LDL, PCSK9 and placental abundances of PCSK9 were significantly higher in MPSH compared to MPH. Circulating PCSK9 levels were correlated with LDL at T3. In MSPH women, the levels of lipid peroxidation and oxidized LDL were significantly higher compared to MPH. LDL isolated from MSPH women presented significantly higher triglycerides and ApoB but lower levels of ApoAI compared to MPH. The formation of conjugated dienes was earlier in LDL from MSPH and in endothelial cells incubated with these LDLs; the levels of reactive oxygen species were significantly higher compared to LDL from MPH. We conclude that increased maternal PCSK9 would contribute to the maternal elevated levels of pro-atherogenic LDL in MSPH, which could eventually be related to maternal vascular dysfunction.

Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with 'Normal' LDL-C Levels.

Residual cardiovascular disease event risk, following statin use and low-density lipoprotein cholesterol (LDL-C) reduction, remains an important and common medical conundrum. Identifying patients with significant residual risk, despite statin drug use, is an unmet clinical need. One pathophysiologic disorder that contributes to residual risk is abnormal distribution in lipoprotein size and density, which is referred to as lipoprotein heterogeneity. Differences in low density lipoprotein (LDL) composition and size have been linked to coronary heart disease (CHD) risk and arteriographic disease progression. The clinical relevance has been investigated in numerous trials since the 1950s. Despite this long history, controversy remains regarding the clinical utility of LDL heterogeneity measurement. Recent clinical trial evidence reinforces the relevance of LDL heterogeneity measurement and the impact on CHD risk prediction and outcomes. The determination of LDL subclass distribution improves CHD risk prediction and guides appropriate treatment.

New targets for treating hypertriglyceridemia.

Elevated fasting and postprandial plasma triglyceride concentrations are associated with an increased risk for atherosclerotic cardiovascular disease in patients on and off low-density lipoprotein (LDL) lowering therapy. This association is not mediated by triglycerides directly. Other components of triglyceride rich lipoproteins, such as cholesterol and apolipoproteins B and -CIII can directly induce and enhance atherosclerosis. In addition, an elevated concentration of triglyceride rich lipoproteins affects the concentration, composition, function, and metabolism of LDL and high-density lipoprotein (HDL), which contributes to the risk. Especially in patients with hypertriglyceridemia, apolipoprotein B and non-HDL-cholesterol (encompassing cholesterol of all atherogenic lipoproteins) predict risk better than LDL-cholesterol and/or triglycerides. Therefore, current guidelines have stated secondary goals relating to non-HDL-cholesterol and apolipoprotein B (in addition to the primary goal relating to LDL-cholesterol). These secondary goals can be achieved by further reducing LDL-cholesterol or by decreasing triglyceride rich lipoproteins. However, only further LDL reduction has so far proven to be beneficial in outcome trials. In addition, high dose eicosapentaenoic acid (EPA) can reduce atherosclerotic cardio-vascular disease risk in patients with hypertriglyceridemia, although benefit is not (or not only) related to apolipoprotein B or non-HDL-cholesterol reduction. Non-HDL-cholesterol and apoB represent novel targets for patients with hypertriglyceridemia, but achieving LDL-cholesterol targets remains the first step for cardio-vascular risk reduction.

The Reciprocal Relationship between LDL Metabolism and Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus and insulin resistance feature substantial modifications of the lipoprotein profile, including a higher proportion of smaller and denser low-density lipoprotein (LDL) particles. In addition, qualitative changes occur in the composition and structure of LDL, including changes in electrophoretic mobility, enrichment of LDL with triglycerides and ceramides, prolonged retention of modified LDL in plasma, increased uptake by macrophages, and the formation of foam cells. These modifications affect LDL functions and favor an increased risk of cardiovascular disease in diabetic individuals. In this review, we discuss the main findings regarding the structural and functional changes in LDL particles in diabetes pathophysiology and therapeutic strategies targeting LDL in patients with diabetes.

Altered properties of plasma low-density lipoprotein (LDL) in ischemic stroke patients with carotid atherosclerosis

Background and Aims: Twenty per cent of ischemic strokes are caused by atherosclerosis from the internal carotid artery. LDL plays an essential role in the development of atherosclerosis. We aimed to compare the composition and modification of plasma LDL isolated from ischemic stroke patients with carotid atherosclerosis and from healthy controls.

Protective Effect of Lusianthridin on Hemin-Induced Low-Density Lipoprotein Oxidation.

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.

Bariatric surgery and LDL cholesterol (BASALTO) trial study protocol: randomised controlled study evaluating the effect of gastric bypass versus sleeve gastrectomy on high LDL cholesterol

IntroductionObservational studies have shown gastric bypass to be superior to sleeve gastrectomy in terms of low-density lipoprotein (LDL) cholesterol improvement. If these results are confirmed in randomised controlled trials, presurgical...

Effect of Supplementation of Several Edible Plant Oils on Nutrient Utilization and Blood Profile of Beef Cattle

Background: In Southeast Asia a high level with the agricultural productivity, especially rice straw is produced for livestock feed such as buffalo and beef cattle. However rice straw is poor quality (low in protein and its high silica content). Subsequently, ruminant nutritionists have established to increase the potential of poor quality roughages for animal feeding such as Total mixed ration (TMR) using rice straw as a roughage source with vegetable oils to increase energy density in the diet, that can improve by produced for ruminant diet. Methods: In this field-laboratory investigation during 2017-2018. Three animals, one and half year old with live weight 120 ± 15.50 kg, were randomly assigned in 3 x 3 latin square design. Each period of feeding lasted for 21 days. During the experimental periods, all cattle were fed total mixed ration (TMR; containing rice straw: concentrate ratio as 40:60), adding soybean oil (SO), palm oil (PO) and sunflower oil (SFO) supplementations. Total fat in TMRs were at 3 percentages. Result: Our investigations were to evaluate the effect of soybean oil (SO), palm oil (PO) and sunflower oil (SFO) supplementations at 3 percentages of total fat in total mixed ration on voluntary feed intake, digestibility, blood profile and fatty acid compositions in the plasma of crossbred Thai native x American Brahman Cattle. The results revealed that treatments did not affect voluntary feed intake (kgDM/head/day; g/KgW0.75) (P is greater than 0.05), but feeding with soybean oil, it was non significantly higher (2.94 kgDM/day). Additionally, nutrient intake and apparent digestibility of organic matter (OM),crude protein (CP), neutral detergent fibre (NDF), acid detergent fibre (ADF) and rumen fermentation except total volatile fatty acids (VFAs) were not affected among all the three treatments, but dry matter (DM) digestibility in soybean and palm oil group animals were recorded significantly higher (P is less than 0.01) than sunflower oil. However blood glucose, blood urea nitrogen, cholesterol, triglyceride, high density lipoprotein and low density lipoprotein and fatty acid composition in plasma were not influenced due to treatments (P is greater than 0.05). Based on this study, feeding beef cattle with SO, PO and SFO should not exceed 3%? in TMR to achieve 7% without any adverse effect on nutrient utilization, rumen fermentation, blood profile and fatty acid compositions in plasma.

Role of Low-Density Lipoprotein in Early Vascular Aging Associated With Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) often have atherosclerotic complications at a young age but normal low-density lipoprotein (LDL) levels. This study was undertaken to investigate the role of LDL composition in promoting early vascular aging in SLE patients. Plasma LDL from 45 SLE patients (SLE-LDL) and from 37 normal healthy controls (N-LDL) was chromatographically divided into 5 subfractions (L1-L5), and the subfraction composition was analyzed. Correlations between subfraction levels and signs of early vascular aging were assessed. Mechanisms of lipid-mediated endothelial dysfunction were explored using in vitro assays and experiments in apoE-/- mice. The L5 percentage was increased 3.4 times in the plasma of SLE patients compared with normal controls. This increased percentage of SLE-L5 was positively correlated with the mean blood pressure (r = 0.27, P = 0.04), carotid intima-media thickness (IMT) (right carotid IMT, r = 0.4, P = 0.004; left carotid IMT, r = 0.36, P = 0.01), pulse wave velocity (r = 0.29, P = 0.04), and blood levels of CD16+ monocytes (r = 0.35, P = 0.004) and CX3CL1 cytokines (r = 0.43, P < 0.001) in SLE patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis revealed that plasma levels of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF) were increased in SLE-LDL and in the SLE-L5 plasma subfraction. Injecting SLE-LDL, SLE-L5, or LPC into young, male apoE-/- mice caused increases in plasma CX3CL1 levels, aortic fatty-streak areas, aortic vascular aging, and macrophage infiltration into the aortic wall, whereas injection of N-LDL or SLE-L1 had negligible effects (n = 3-8 mice per group). In vitro, SLE-L5 lipid extracts induced increases in CX3CR1 and CD16 expression in human monocytes; synthetic PAF and LPC had similar effects. Furthermore, lipid extracts of SLE-LDL and SLE-L5 induced the expression of CX3CL1 and enhanced monocyte-endothelial cell adhesion in assays with bovine aortic endothelial cells. An increase in plasma L5 levels, not total LDL concentration, may promote early vascular aging in SLE patients, leading to premature atherosclerosis.

Impact of Obesity on Castelli’s Risk Index I and II, in Young Adult Females

Background: Obesity is one of today’s most blatantly visible, yet most neglected, public health problems. In 2016, 39% of adults worldwide were overweight. Fueled by economic growth, urbanization, an increasingly sedentary lifestyle, and a nutritional transition to processed foods and high calorie diets over the last 30 years, many countries have witnessed the prevalence of obesity in its citizens double, and even quadruple. Obesity especially visceral obesity causes insulin resistance and is associated with dyslipidemia, impaired glucose metabolism, and hypertension all of which exacerbate atherosclerosis, and are risk factors for developing cardiovascular diseases (CVD). The primary dyslipidemia related to obesity is characterized by increased total cholesterol (TC), decreased high density lipoprotein (HDL) levels and abnormal low density lipoprotein (LDL) composition. Lipoprotein ratios are becoming increasingly popular as a way to predict atherosclerosis and CVD. Aims and Objectives: The present study was undertaken to assess the impact of overweight/obesity on lipid profile parameters and lipoprotein ratios- Castelli’s Risk Index I and II, in young adult females. Materials and Method: The present study was conducted in KIMS, Hubli, the study and its conduct was cleared by the Ethical committee. Sixty apparently healthy young females were selected for the study. Health status and other personal data were obtained via comprehensive questionnaire. The subjects were divided into two groups based on BMI; Healthy (BMI 18.5-24.99) and Overweight (BMI > 25). Lipid profile was evaluated and lipoprotein ratios calculated. Comparison between the two groups was done using students’ t-test. Results: Values for Castelli’s Risk Index I & II were found to be significantly higher in the overweight group compared to the control group. Conclusion: Obesity leads to an unfavorable lipid pattern and raises values of both Castelli’s Risk Index I & II.

Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model

Chemotherapeutic agents used in cancer treatment associated to nanoparticles (LDE) that mimic the composition of low-density lipoprotein and buffer their toxicity can have strong anti-atherosclerosis action, as we showed in cholesterol-fed rabbits. Here, a novel preparation of docetaxel (DTX) carried in LDE was evaluated. Eighteen rabbits were fed 1% cholesterol during 8 weeks. After the first 4 weeks, 9 animals were treated for 4 weeks with intravenous LDE-DTX (1 mg/kg/week) and 9 with LDE only (controls) once a week for 4 weeks. Animals were then euthanized and the aortas were analyzed for morphometry, immunohistochemistry and Western blot. LDE-DTX treated group showed 80% reduction of atheroma area compared to controls. LDE-DTX treatment reduced in 60% the protein expression of macrophage marker CD68 and of MCP-1 in 80%. LDE-DTX pronouncedly lowered expression of pro-inflammatory markers NF-κB, TNF-α, IL-1β, IL-6 and von Willebrand factor and elicited 40% reduction in cell proliferation marker PCNA. The presence of smooth muscle cells in the intima was 85% smaller than in controls. Pro-apoptotic caspase 3, caspase 9, Bax, and anti-apoptotic Bcl-2 all were reduced by LDE-DTX. Protein expression of MMP-2 and MMP-9, TGF-β, and collagen 1 and 3 were also markedly lowered by the LDE-DTX treatment. Animals showed no hematological, hepatic or renal toxicity consequent to LDE-DTX treatment. In conclusion, LDE-DTX showed a wide array of strong effects on pro-inflammatory and proliferation-promoting factors that drive the lesion development. These findings and the lack of observable toxicity indicate that LDE-DTX can be a candidate for future clinical trials.

FEATURES OF FUNCTIONAL STATE OF THE LIVER IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS DEPENDING ON THE PRESENCE OF COMORBID ARTERIAL HYPERTENSION OF THE II-ND STAGE AND I-ST DEGREE OF OBESITY

Objective. To investigate the features of the comorbid flow of non-alcoholic steatohepatitis (NASH) in patients with hypertension (HTN), specifically the state of the lipid spectrum of blood and glycemia.Material and methods. 120 patients with NASH and comorbid HTN of the II stage were examined, including: 60 patients with NASH and HTN of the II stage with normal body weight - group 1, 60 patients with NASH with comorbid HTN II stage, and Obesity I degree - Group 2. The control group consisted of 20 practically healthy persons (PHPs) of the corresponding age and sex.Results. At a comorbid flow of NASH with HTN and obesity, a deeper lipid imbalance (hypertriglyceridemia (2.1 times, p <0.05)), hypercholesterolemia (1.5 times, p <0.05), including in the composition of low density lipoprotein (1.8 times, p <0.05), decrease in the content of high density lipoprotein (1.8 times, p <0.05), increase in the atherogenic index (2.7 times, p <0,05). The reason for the progression of metabolic syndrome against a background of NASH and HTN is a lipid distress syndrome with an increase of cholesterol in the blood, proatherogenic LDL, and a deficiency of anti-atherogenic HDL. Conclusions. Based on the above mentioned data, the most important prerequisites for the development of NASH against a background of obesity and HTN are likely postprandial hyperglycemia, hyperinsulinemia, increased glycosylated hemoglobin, and primary tissue Insulin resistance.

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study

BackgroundThe association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. MethodsDirect measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. ResultsThe geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ± 3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. ConclusionsMedium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD.

The effect of black seed powder on blood glycaemia, blood lipidemia and body composition on adults at risk for cardiovascular diseases: A con-trolled, randomized, single blind, parallel-design study

Recently 42% of the population in the United Arab Emirates (UAE) was diagnosed with metabolic syndrome (MetS), while the prevalence of the MetS in the Gulf Cooperation Council Countries (GCC) is 10-15% higher than in the most developed countries, with generally higher prevalence rates for women. Recent studies proved that black seed may have an effect in reducing the metabolic syndrome factors as well as the cardiovascular diseases risk factors. More studies proved the anti-lipidemic and anti-glycemic effects of blackseed; therefore, it could be used for the management and prevention of the MetS problems. Objectives: To measure the effect of blackseed powder on fasting blood glucose (FBG), hemoglobin (Hb), hemoglobin A1c (HbA1c), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), blood pressure (BP), waist circumference (WC) and body composition in participants at risk for cardiovascular diseases. Methodology: The study is a controlled, randomized, single blind, parallel-design study. 60 participants who are at risk for cardiovascular diseases were randomly distributed into 2 treatment groups, the first group was the blackseed powder group while the second group was a placebo-control (corn starch) group. 3 grams per day of each treatment was ingested by the participants for 12 weeks. Results: 51 participants continued the study from both groups (29 black seed, 22 Placebo), there was a significant improvement in Cholesterol, HDL, LDL, Triglyceride levels, WC and the percent of body fat (P-value &lt; 0.05). While it showed no effect on systolic and diastolic blood pressure levels and blood glucose levels for the black seed group compared to the placebo group. Conclusion: Black seed powder has a significant effect on improving Blood lipids levels in blood, WC and percent of body fat while it showed no improvement in blood glucose levels as well as blood pressure levels for individuals at risk for CVD.

LDL fatty acids composition as a risk biomarker of cardiovascular disease

ObjectiveFatty acid composition of Low-density lipoprotein (LDL) particle is an effective factor in LDL oxidation and atherosclerotic plaques formation. This study evaluates the relationship between LDL fatty acid composition and coronary artery disease (CAD). Methods42 men with coronary artery disease (CAD-group) and 40 men without coronary artery disease (non-CAD-group) were selected. LDL fatty acid composition of blood samples was measured by gas chromatography. ResultsOx-LDL was significantly high in CAD-group. Poly unsaturated fatty acids (PUFA) and PUFA/MUFA (Mono unsaturated fatty acids), linoleic acid and arachidonic acid were significantly higher in CAD-group than in non-CAD-group. In CAD-group, a reverse correlation was observed between oleic acid concentrations and ox-LDL levels and a direct correlation was seen between arachidonic acid concentrations and ox-LDL levels. ConclusionComposition of LDL is related to atherosclerosis and CAD. High levels of arachidonic and linoleic acids could increase LDL oxidation and atherosclerotic plaques formation. In addition, LDL arachidonic acid levels could be a better predictor of CAD.

Modeling Small-Angle X-ray Scattering Data for Low-Density Lipoproteins: Insights into the Fatty Core Packing and Phase Transition.

Atherosclerosis and its clinical consequences are the leading cause of death in the western hemisphere. While many studies throughout the last decades have aimed at understanding the disease, the clinical markers in use today still fail to accurately predict the risks. The role of the current main clinical indicator, low density lipoprotein (LDL), in depositing fat to the vessel wall is believed to be the onset of the process. However, many subfractions of the LDL, which differ both in structure and composition, are present in the blood and among different individuals. Understanding the relationship between LDL structure and composition is key to unravel the specific role of various LDL components in the development and/or prevention of atherosclerosis. Here, we describe a model for analyzing small-angle X-ray scattering data for rapid and robust structure determination for the LDL. The model not only gives the overall structure but also the particular internal layering of the fats inside the LDL core. Thus, the melting of the LDL can be followed in situ as a function of temperature for samples extracted from healthy human patients and purified using a double protocol based on ultracentrifugation and size-exclusion chromatography. The model provides information on: (i) the particle-specific melting temperature of the core lipids, (ii) the structural organization of the core fats inside the LDL, (iii) the overall shape of the particle, and (iv) the flexibility and overall conformation of the outer protein/hydrophilic layer at a given temperature as governed by the organization of the core. The advantage of this method over other techniques such as cryo-TEM is the possibility of in situ experiments under near-physiological conditions which can be performed relatively fast (minutes at home source, seconds at synchrotron). This approach now allows the monitoring of structural changes in the LDL upon different stresses from the environment, such as changes in temperature, oxidation, or external agents used or currently in development against atherosclerotic plaque build-up and which are targeting the LDL.

Carbohydrate composition of circulating multiple-modified low-density lipoprotein.

Atherogenic modification of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis, as modified LDL, but not native LDL, induces pronounced accumulation of cholesterol and lipids in the arterial wall. It is likely that LDL particles undergo multiple modifications in human plasma: desialylation, changes in size and density, acquisition of negative electric charge, oxidation, and complex formation. In a total LDL preparation isolated from pooled plasma of patients with coronary atherosclerosis and from healthy subjects, two subfractions of LDL could be identified: desialylated LDL bound by a lectin affinity column and normally sialylated (native) LDL that passed through the column. The desialylated LDL subfraction therefore represents circulating modified LDL. In this work, we performed a careful analysis of LDL particles to reveal changes in the composition of glycoconjugates associated with proteins and lipids. Protein fraction of LDL from atherosclerotic patients contained similar amounts of glucosamine, galactose, and mannose, but a 1.6-fold lower level of sialic acid as compared to healthy donors. Lipid-bound glycoconjugates of total LDL from patients with coronary atherosclerosis contained 1.5–2-fold less neutral monosaccharides than total LDL from healthy donors. Patient-derived LDL also contained significantly less sialic acid. Our results demonstrate that carbohydrate composition of LDL from atherosclerotic patients was altered in comparison to healthy controls. In particular, prominent decrease in the sialic acid content was observed. This strengthens the hypothesis of multiple modification of LDL particles in the bloodstream and underscores the clinical importance of desialylated LDL as a possible marker of atherosclerosis progression.