Interplay between lipoproteins, the complement system and blood cells in atherosclerosis

Er is toenemend bewijs dat het niet noodzakelijk is om cholesterol en vetzuren in nuchtere toestand te meten, maar dat een niet-nuchtere meting in de meeste gevallen ook kan volstaan. De ontwikkeling van aderverkalking is complex en gaat veel verder dan alleen het cholesterolgehalte in het bloed. Aderverkalking, vet- en cholesterolstofwisseling en het immuunsysteem inclusief rode bloedcellen zijn nauw met elkaar verbonden. Hierbij lijkt het immuunsysteem zowel schadelijk als beschermend tegen de ontwikkeling van aderverkalking te kunnen werken. Vitamine D kan deels de schadelijke activatie van witte bloedcellen na vetinname voorkomen en heeft een gunstig effect op de elasticiteit van de slagaders. Rode bloedcellen kunnen juist een beschermend effect uitoefenen op de vaatwand door middel van transport van schadelijke cholesterolpakketjes. Dit transportmechanisme kan mogelijk plaatsvinden door middel van het niet-specifieke immuunsysteem met de complement receptor 1 danwel op basis van de ABO bloedgroep of een combinatie van beideUBL - phd migration 201

Closed Type Families with Overlapping Equations

Open, type-level functions are a recent innovation in Haskell that move Haskell towards the expressiveness of dependent types, while retaining the look and feel of a practical programming language. This paper shows how to increase expressiveness still further, by adding closed type functions whose equations may overlap, and may have non-linear patterns over an open type universe. Although practically useful and simple to implement, these features go be- yond conventional dependent type theory in some respects, and have a subtle metatheory

Understanding Postprandial Inflammation and Its Relationship to Lifestyle Behaviour and Metabolic Diseases

Postprandial hyperlipidemia with accumulation of remnant lipoproteins is a common metabolic disturbance associated with atherosclerosis and vascular dysfunction, particularly during chronic disease states such as obesity, the metabolic syndrome and, diabetes. Remnant lipoproteins become attached to the vascular wall, where they can penetrate intact endothelium causing foam cell formation. Postprandial remnant lipoproteins can activate circulating leukocytes, upregulate the expression of endothelial adhesion molecules, facilitate adhesion and migration of inflammatory cells into the subendothelial space, and activate the complement system. Since humans are postprandial most of the day, the continuous generation of remnants after each meal may be one of the triggers for the development of atherosclerosis. Modulation of postprandial lipemia by lifestyle changes and pharmacological interventions could result in a further decrease of cardiovascular mortality and morbidity. This paper will provide an update on current concepts concerning the relationship between postprandial lipemia, inflammation, vascular function, and therapeutic options

Soundness of Unravelings for Conditional Term Rewriting Systems via Ultra-Properties Related to Linearity

Unravelings are transformations from a conditional term rewriting system (CTRS, for short) over an original signature into an unconditional term rewriting systems (TRS, for short) over an extended signature. They are not sound w.r.t. reduction for every CTRS, while they are complete w.r.t. reduction. Here, soundness w.r.t. reduction means that every reduction sequence of the corresponding unraveled TRS, of which the initial and end terms are over the original signature, can be simulated by the reduction of the original CTRS. In this paper, we show that an optimized variant of Ohlebusch's unraveling for a deterministic CTRS is sound w.r.t. reduction if the corresponding unraveled TRS is left-linear or both right-linear and non-erasing. We also show that soundness of the variant implies that of Ohlebusch's unraveling. Finally, we show that soundness of Ohlebusch's unraveling is the weakest in soundness of the other unravelings and a transformation, proposed by Serbanuta and Rosu, for (normal) deterministic CTRSs, i.e., soundness of them respectively implies that of Ohlebusch's unraveling.Comment: 49 pages, 1 table, publication in Special Issue: Selected papers of the "22nd International Conference on Rewriting Techniques and Applications (RTA'11)

Dyslipidemia in Obesity: Mechanisms and Potential Targets

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39 ± 8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02 ± 6.20 mM*h/L) (P < 0.05). Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism

Erythrocyte-Bound Apolipoprotein B in Relation to Atherosclerosis, Serum Lipids and ABO Blood Group

Introduction:Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB) are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms.Methods:Subjects with and without CVD were included (N = 398). Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT) was determined as a measure of (subclinical) atherosclerosis.Results:Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80±0.09 mm, N = 140) compared to subjects with a normal CIMT (0.57±0.08 mm, N = 258) (P = 0.007, adjusted P<0.001). CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021). A total of 55 subjects (13.6%) were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82). Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56±0.94 a.u.) when compared to subjects with blood group A (0.89±1.15 a.u), blood group B (0.73±0.1.12 a.u.) or blood group AB (0.69±0.69 a.u.) (P-ANOVA = 0.002).Conclusion:Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant

Association of cardiovascular risk factors with carotid intima media thickness in patients with rheumatoid arthritis with low disease activity compared to controls: A cross-sectional study

Objectives Rheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA. Methods Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound. Results In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQ