Publications by authors named "Niels Nijstad"

Atherosclerotic cardiovascular disease (CVD) represents the largest cause of mortality in end-stage renal disease (ESRD). CVD in ESRD is not explained by classical CVD risk factors such as HDL cholesterol mass levels making functional alterations of lipoproteins conceivable. HDL functions in atheroprotection by promoting reverse cholesterol transport (RCT), comprising cholesterol efflux from macrophage foam cells, uptake into hepatocytes and final excretion into the feces.

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Aims: Altered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets relevant to atherosclerosis.

Methods And Results: LDL receptor deficient mice that were transplanted with Sgpl1(-/-) bone marrow showed disrupted S1P gradients translating into lymphopenia and abrogated lymphocyte mitogenic and cytokine response as compared to controls.

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Cholesteryl ester transfer protein (CETP) activity results in a proatherogenic lipoprotein profile. In cholestatic conditions, farnesoid X receptor (FXR) signaling by bile acids (BA) is activated and plasma HDL cholesterol (HDL-C) levels are low. This study tested the hypothesis that FXR-mediated induction of CETP contributes to this phenotype.

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Type I diabetes mellitus (T1DM) increases atherosclerotic cardiovascular disease; however, the underlying pathophysiology is still incompletely understood. We investigated whether experimental T1DM impacts HDL-mediated reverse cholesterol transport (RCT). C57BL/6J mice with alloxan-induced T1DM had higher plasma cholesterol levels (P < 0.

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Microsomal triglyceride transfer protein (MTP) facilitates the transport of dietary and endogenous fat by the intestine and liver by assisting in the assembly and secretion of triglyceride-rich apolipoprotein B-containing lipoproteins. Higher concentrations of apolipoprotein B lipoproteins predispose individuals to various cardiovascular and metabolic diseases such as atherosclerosis, diabetes, obesity and the metabolic syndrome. These can potentially be avoided by reducing MTP activity.

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Apolipoprotein (apo) O is a newly discovered apolipoprotein preferentially contained within HDL; however, currently, no data are available on the (patho)physiological effects of apoO. Therefore, the present study assessed the impact of apoO overexpression on (i) plasma lipids and lipoproteins as well as on (ii) HDL functionality. Human apoO was overexpressed by means of recombinant adenovirus (AdhapoO) in human apoA-I transgenic mice, a humanized mouse model of HDL metabolism.

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Background & Aims: High-density lipoproteins (HDLs) protect against atherosclerotic cardiovascular disease, mainly by promoting reverse cholesterol transport (RCT). Biliary sterol secretion supposedly represents the final step in RCT, but the relevance of this pathway has not been explored. We tested the dependency of RCT on functional biliary sterol secretion.

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Unlabelled: A major atheroprotective functionality of high-density lipoproteins (HDLs) is to promote "reverse cholesterol transport" (RCT). In this process, HDLs mediate the efflux and transport of cholesterol from peripheral cells and its subsequent transport to the liver for further metabolism and biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y(13) (purinergic receptor P2Y, G protein-coupled, 13) activation is essential for HDL uptake but the potential of P2Y(13) as a target to promote RCT has not been documented.

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Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT).

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Atherosclerosis is linked to inflammation. HDL protects against atherosclerotic cardiovascular disease, mainly by mediating cholesterol efflux and reverse cholesterol transport (RCT). The present study aimed to test the impact of acute inflammation as well as selected acute phase proteins on RCT with a macrophage-to-feces in vivo RCT assay using intraperitoneal administration of [(3)H]cholesterol-labeled macrophage foam cells.

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Scavenger receptor BI (SR-BI) is a selective uptake receptor for HDL cholesterol but is also involved in the catabolism of apolipoprotein (apo)B-containing lipoproteins. However, plasma levels of apoB-containing lipoproteins increase following hepatic SR-BI overexpression, suggesting that SR-BI not solely mediates their catabolism. We therefore tested the hypothesis that hepatic SR-BI impacts on VLDL production.

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Unlabelled: Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesterol from high-density lipoprotein (HDL) particles by the liver and influences biliary cholesterol secretion. However, it is not clear, if this effect is direct or indirect. The aim of this study was to determine the impact of SR-BI on biliary cholesterol secretion, especially in a functional context with ATP-binding cassette transporter g5 (Abcg5)/Abcg8 and Abcb4.

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Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1 deficiency on plasma HDL, liver cholesterol metabolism and biliary cholesterol secretion under conditions of feeding either chow or a 1% cholesterol diet (HCD) or treatment with the LXR agonist T0901317.

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High density lipoprotein cholesterol is thought to represent a preferred source of sterols secreted into bile following hepatic uptake by scavenger receptor class B type I (SR-BI). The present study aimed to determine the metabolic effects of an endothelial lipase (EL)-mediated stimulation of HDL cholesterol uptake on liver lipid metabolism and biliary cholesterol secretion in wild-type, SR-BI knockout, and SR-BI overexpressing mice. In each model, injection of an EL expressing adenovirus decreased plasma HDL cholesterol (P < 0.

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Endothelial lipase (EL) is a negative regulator of high density lipoprotein (HDL) cholesterol plasma levels, and scavenger receptor BI (SR-BI) is involved in remodeling of HDL. The present study investigates the requirement of SR-BI for the effects of EL-mediated phospholipid hydrolysis on HDL metabolism in vivo. In vitro, selective uptake from EL-modified HDL was 129% higher than selective uptake from control HDL in SR-BI-overexpressing cells (p=0.

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High density lipoprotein cholesterol represents a major source of biliary cholesterol. Secretory phospholipase A2 (sPLA2) is an acute phase enzyme mediating decreased plasma HDL cholesterol levels. Clinical studies reported a link between increased sPLA2 expression and the presence of cholesterol gallstones.

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Enterohaemorrhagic Escherichia coli (EHEC) is an important food-borne pathogen that, upon infection, causes destruction of the microvilli brush border of intestinal cells. EHEC is able to recruit several host cell proteins and induce actin accumulation beneath its adherence site, forming a pedestal-like structure upon which the bacterium is firmly attached. Injection of bacterial effectors into the host cells is required to trigger the recruitment and activation of proteins, such as cortactin, neural Wiskott-Aldrich syndrome protein (N-WASP) and Arp2/3 complex, directly involved in the actin polymerization process.

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Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are important human pathogens. Upon attachment to host cells, EPEC and EHEC are able to induce actin polymerization, which accumulates, forming a pedestal-like structure beneath the attached bacteria.

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The ATPase SecA provides the driving force for the transport of secretory proteins across the cytoplasmic membrane of Escherichia coli. SecA exists as a dimer in solution, but the exact oligomeric state of SecA during membrane binding and preprotein translocation is a topic of debate. To study the requirements of oligomeric changes in SecA during protein translocation, a non-dissociable SecA dimer was formed by oxidation of the carboxyl-terminal cysteines.

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