189,748 research outputs found

    Transport of apolipoproteins A-I and A-II by human thoracic duct lymph

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    The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in 2 subjects before and 3 subjects after renal transplantation. Lymph triglyceride transport was ~83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659±578 mg/d for apolipoprotein A-I and 109±59 mg/d for apolipoprotein A-II among the 5 subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine. Lymph high density lipoprotein particles are mostly high density lipoprotein(2b) and high density lipoprotein(2a) and have a greater overall relative triglyceride content and a smaller relative cholesteryl ester content when compared with homologous plasma high density lipoproteins. The major quantity of both lymph apolipoprotein A-I (81±8%) and apolipoprotein A-II (90±11%) was found within high density lipoproteins with almost all of the remainder found in chylomicrons and very low density lipoproteins. The combined results are consistent with a major contribution of the intestine to total body synthesis of apolipoprotein A-I and apolipoprotein A-II. An important role of lymph in returning filtered apolipoprotein to plasma in association with high density lipoproteins is proposed. Accompanying the return of filtered apolipoprotein to the plasma is a probable transformation, both in size and composition, of at least some of the lymph high density lipoprotein(2b) and high density lipoprotein(2a) particles into high density lipoprotein3

    Influence of different fat emulsions with 10 or 20% MCT/LCT or LCT on lipoproteins in plasma of patients after abdominal surgery

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    In patients after elective abdominal surgery, different fat emulsions were used to compare their efficacy in total parenteral nutrition and in normalizing plasma lipoprotein levels. In five different groups with 5 patients each, half of the nonprotein calories were given as medium-chain triglycerides/ long-chain triglycerides (1:1) or as long-chain triglycerides alone in 10 or 20% fat emulsions or as glucose alone in a control group for 7 days. After surgery, an initial decrease of all plasma lipoprotein components was followed by a different behavior of glyceride-glycerol, cholesterol, phospholipids, and apolipoproteins. Glyceride-glycerol in very-low-density lipoproteins and high-density lipoproteins is increasing during infusion of fat emulsions and decreasing during overnight interruption of infusions. After the 7-day infusion period, there was no significant difference in very-low-density lipoprotein glyceride-glycerol as compared with the values before different infusions, Low-density lipoprotein cholesterol is reaching and exceeding preoperative concentrations between the 4th and the 7th day, most during infusion of 10% fat emulsion and especially due to an increase of free cholesterol, High-density lipoprotein cholesterol and apolipoprotein A-I reach preoperative levels during infusion of fat emulsions but not with glucose alone, Higher than preoperative values are reached in phospholipids with all fat infusions already on day 4, Abnormal lipoprotein X occurred least with the medium-chain/long-chain triglyceride 20% fat-infusion. This fat emulsion is suggested as having the best normalizing effect on plasma lipoproteins and best tolerance in patients after surgery

    Causal relevance of blood lipid fractions in the development of carotid atherosclerosis: Mendelian randomization analysis.

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    BACKGROUND: Carotid intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with risk of coronary heart disease events. Statins reduce progression of CIMT and coronary heart disease risk in proportion to the reduction in low-density lipoprotein cholesterol. However, interventions targeting triglycerides (TGs) or high-density lipoprotein cholesterol (HDL-C) have produced inconsistent effects on CIMT and coronary heart disease risk, making it uncertain whether such agents are ineffective for coronary heart disease prevention or whether CIMT is an inadequate marker of HDL-C or TG-mediated effects. We aimed to determine the causal association among the 3 major blood lipid fractions and common CIMT using mendelian randomization analysis. METHODS AND RESULTS: Genetic scores specific for low-density lipoprotein cholesterol, HDL-C, and TGs were derived based on single nucleotide polymorphisms from a gene-centric array in ≈5000 individuals (Cardiochip scores) and from a genome-wide association meta-analysis in >100 000 individuals (Global Lipids Genetic Consortium scores). These were used as instruments in a mendelian randomization analysis in 2 prospective cohort studies. A genetically predicted 1 mmol/L higher low-density lipoprotein cholesterol concentration was associated with a higher common CIMT by 0.03 mm (95% confidence interval, 0.01-0.04) and 0.04 mm (95% confidence interval, 0.02-0.06) based on the Cardiochip and Global Lipids Genetic Consortium scores, respectively. HDL-C and TGs were not causally associated with CIMT. CONCLUSIONS: Our findings confirm a causal relationship between low-density lipoprotein cholesterol and CIMT but not with HDL-C and TGs. At present, the suitability of CIMT as a surrogate marker in trials of cardiovascular therapies targeting HDL-C and TGs is questionable and requires further study

    An integrated mathematical model of cellular cholesterol biosynthesis and lipoprotein metabolism

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    Cholesterol regulation is an important aspect of human health. In this work we bring together and extend two recent mathematical models describing cholesterol biosynthesis and lipoprotein endocytosis to create an integrated model of lipoprotein metabolism in the context of a single hepatocyte. The integrated model includes a description of low density lipoprotein (LDL) receptor and cholesterol synthesis, delipidation of very low density lipoproteins (VLDLs) to LDLs and subsequent lipoprotein endocytosis. Model analysis shows that cholesterol biosynthesis produces the majority of intracellular cholesterol. The availability of free receptors does not greatly effect the concentration of intracellular cholesterol, but has a detrimental effect on extracellular VLDL and LDL levels. We test our model by considering its ability to reproduce the known biology of Familial Hypercholesterolaemia and statin therapy. In each case the model reproduces the known biological behaviour. Quantitative differences in response to statin therapy are discussed in the context of the need to extend the work to a more {\it in vivo} setting via the incorporation of more dietary lipoprotein related processes and the need for further testing and parameterisation of {\it in silico} models of lipoprotein metabolism

    Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy.

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    OBJECTIVE: The association between cholesterol and endothelial dysfunction remains controversial. We tested the hypothesis that lipoprotein subclasses are associated with coronary endothelial dysfunction. METHODS AND RESULTS: Coronary endothelial function was assessed in 490 patients between November 1993 and February 2007. Fasting lipids and nuclear magnetic resonance (NMR) lipoprotein particle subclasses were measured. There were 325 females and 165 males with a mean age of 49.8+/-11.6 years. Coronary endothelial dysfunction (epicardial constriction>20% or increase in coronary blood flow<50% in response to intracoronary acetylcholine) was diagnosed in 273 patients, the majority of whom (64.5%) had microvascular dysfunction. Total cholesterol and LDL-C (low density lipoprotein cholesterol) were not associated with endothelial dysfunction. One-way analysis and multivariate methods adjusting for age, gender, diabetes, hypertension and lipid-lowering agent use were used to determine the correlation between lipoprotein subclasses and coronary endothelial dysfunction. Epicardial endothelial dysfunction was significantly correlated with total (p=0.03) and small LDLp (LDL particles) (p<0.01) and inversely correlated with total and large HDLp (high density lipoprotein particles) (p<0.01). CONCLUSIONS: Epicardial, but not microvascular, coronary endothelial dysfunction was associated directly with LDL particles and inversely with HDL particles, suggesting location-dependent impact of lipoprotein particles on the coronary circulation

    Alterations of intestinal lipoprotein metabolism in diabetes mellitus and metabolic syndrome

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    Diabetes and metabolic syndrome are associated with abnormal postprandial lipoprotein metabolism, with a significant delay in the clearance of many lipid parameters, including triglycerides and chylomicrons. Abnormal concentrations of plasma lipids can result from changes in the production, conversion, or catabolism of lipoprotein particles. Whereas the liver is involved in controlling serum lipid levels through synthesis of liver derived triglyceride-rich lipoproteins and low-density lipoprotein metabolism, the intestine also has a major role in lipoprotein production. Postprandial lipemia results from increases in apoB-48 availability, lipogenesis, and the synthesis and absorption of cholesterol in the enterocytes. Increased intestinal lipoprotein production prolongs postprandial lipemia in patients with diabetes and MetS, and may contribute directly to atherogenesis in these patients

    Identification of a residue in hepatitis C virus E2 glycoprotein that determines scavenger receptor BI and CD81 receptor dependency and sensitivity to neutralizing antibodies.

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    Hepatitis C virus (HCV) infection is dependent on at least three coreceptors: CD81, scavenger receptor BI (SR-BI), and claudin-1. The mechanism of how these molecules coordinate HCV entry is unknown. In this study we demonstrate that a cell culture-adapted JFH-1 mutant, with an amino acid change in E2 at position 451 (G451R), has a reduced dependency on SR-BI. This altered receptor dependency is accompanied by an increased sensitivity to neutralization by soluble CD81 and enhanced binding of recombinant E2 to cell surface-expressed and soluble CD81. Fractionation of HCV by density gradient centrifugation allows the analysis of particle-lipoprotein associations. The cell culture-adapted mutation alters the relationship between particle density and infectivity, with the peak infectivity occurring at higher density than the parental virus. No association was observed between particle density and SR-BI or CD81 coreceptor dependence. JFH-1 G451R is highly sensitive to neutralization by gp-specific antibodies, suggesting increased epitope exposure at the virion surface. Finally, an association was observed between JFH-1 particle density and sensitivity to neutralizing antibodies (NAbs), suggesting that lipoprotein association reduces the sensitivity of particles to NAbs. In summary, mutation of E2 at position 451 alters the relationship between particle density and infectivity, disrupts coreceptor dependence, and increases virion sensitivity to receptor mimics and NAbs. Our data suggest that a balanced interplay between HCV particles, lipoprotein components, and viral receptors allows the evasion of host immune responses

    Importance of measuring non-HDL cholesterol in type 2 diabetes patients.

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    OBJECTIVE: To study the correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol in patients with Type 2diabetes mellitus and the proportion of patients achieving Adult Treatment Panel III recommended goals. METHODS: The cross sectional study was conducted at the Diabetic Clinic, Aga Khan University Hospital, Karachi. Data of Type 2 diabetesmellitus patients who attended the clinic bewteen 2007 and 2011 was reviewed. All Type 2 diabetic patients of either gender with fasting lipid profile irrespective of taking lipid lowering therapy were included.Type-1 DM, gestational diabetes, type 2 diabetes patients with pregnancy and those with incomplete data were excluded. Correlation between the low-density lipoprotein and Non-high-density lipoprotein was assessed by applying Cramer V and phi. Proportion of patients achieving Adult Treatment Panel III recommended goals was checked. Multivariable regression was done to identify common factors associated with elevated Non-high-density lipoprotein cholesterol. RESULTS: A total of 1352 patients fulfilling the eligibility criteria were included in the study. Mean age of the patients was 54.5 +/- 11.3 years; 797 (59%) were males; 1122 (83%) had Body Mass Index above 25; and 1016 (75%) had HbA1c \u3e or = 7%. Mean Non-high-density lipoprotein cholesterol was 129 +/- 42 mg/dl. Mean low-density lipoprotein cholesterol was 100 +/- 37 mg/dl. Both low-density lipoprotein \u3c or = 100 and Non-HDL \u3c or = 130 mg/dl was achieved in 645 (48%) patients. It is important to note that although 728 (53.8%) patients achieved target LDL cholesterol of \u3c or = 100 mg/dl, among them 83 (11.4%) had Non-high-density lipoprotein cholesterol still above the target \u3e 130 mg/dl (p \u3c 0.05). Out of 752 patients with Non-high-density lipoprotein cholesterol \u3c or = 130 mg/dl, 645 (86%) had low-density lipoprotein cholesterol below 100 mg/dl. Cramer V and Phi showed that correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol was 0.71 (p value \u3c 0.01). After adjusting for other covariates, low-density lipoprotein cholesterol \u3e 100 mg/dl was independently associated with having Non-high-density lipoprotein cholesterol \u3e 130 mg/dl (Adjusted Odds Ratio 38.6; 95% Confidance Interval = 28.1-53.1). Similarly, age \u3c or = 60 years was 60% more likely to have Non-high-density lipoprotein cholesterol \u3e 130 mg/dl (Adjusted Odds Ratio 1.6; 95% Confidance Interval = 1.01 - 2.3). Whereas having obesity Body Mass Index \u3e 25 was 3.6 times more associated to have Non-high-density lipoprotein \u3e 130 mg/dl (Adjusted Odds Ratio 3.6; 95% Confidance Interval = 1.6-7.7). In patients with coronary artery disease, combined goal achievement of low-density lipoprotein \u3c or = 70 mg/dl and Non-high-density lipoprotein cholesterol \u3c or = 100 mg/dl was seen in 59 (35%). Among patients with high-density lipoprotein \u3c or = 70 mg/dl, 8 (10%) had Non-high-density lipoprotein \u3e 100 mg/dl (p \u3c 0.05). CONCLUSION: The study showed a correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol. As measuringNon-high-density lipoprotein cholesterol in Type 2 DM patients is simple, cost-effective and convenient because it does not require 12-hour fasting which may be a risk for hypoglycaemia in these patients, clinicians may choose Non-high-density lipoprotein as a routine measure in everyday practice

    Perbandingan Kadar Low Density Lipoprotein dan High Density Lipoprotein Antara Akseptor KB Pil Kombinasi Dengan Depo Medroksiprogesteron Asetat

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    More than six million women worldwide use contraceptive injection and the popular contraceptive method used is contraceptive pill. Combined pill contraceptives have side effects, which are increased triglyceride and total cholesterol levels and changes in carbohydrate metabolism while the DMPA is irregular menstruation/amenorrhea, weight changes and lipid changes.This research is an observational with Cross Sectional Comparative approach to 36 combination pill acceptor and 36 DMPA acceptor. This study was conducted ini the area of Andalas and Lubuk Buaya Health Center. The sampling method used in this research was simple random sampling method. The analysis was used T-Independent test. The results showed that Low Density Lipoprotein levels DMPA (63,97 ± 12,75 mg/dl) vs combined contraceptive pill (89,66 ± 28,39 mg/dl) p = 0,25 and High Density Lipoprotein levels DMPA (63,97± 12,75 mg/dl) vs combined contraceptive pill (60,06 ± 15,57 mg/dl), p = 0,25. Results of this study concluded that there was significant difference in average of Low Density Lipoprotein and High Density Lipoprotein levels in the combined contraceptive pill and Medroxy Progesteron Acetate Depot acceptor but statistically the difference was no significant
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