Correction: Vascular Endothelial Growth Factor Receptor-2 Couples Cyclo-Oxygenase-2 with Pro-Angiogenic Actions of Leptin on Human Endothelial Cells.

[This corrects the article DOI: 10.1371/journal.pone.

Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway.

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs-artificial TG-rich CMR-like particles (A-CRLPs)-containing TGs extracted from fish, DHA-rich algal, corn, or palm oils.

The Emerging Role of Disturbed CoQ Metabolism in Nonalcoholic Fatty Liver Disease Development and Progression.

Although non-alcoholic fatty liver disease (NAFLD), characterised by the accumulation of triacylglycerol in the liver, is the most common liver disorder, the causes of its development and progression to the more serious non-alcoholic steatohepatitis (NASH) remain incompletely understood. Oxidative stress has been implicated as a key factor in both these processes, and mitochondrial dysfunction and inflammation are also believed to play a part. Coenzyme Q (CoQ) is a powerful antioxidant found in all cell membranes which has an essential role in mitochondrial respiration and also has anti-inflammatory properties.

Postprandial phase time influences the uptake of TAG from postprandial TAG-rich lipoproteins by THP-1 macrophages.

Postprandial TAG-rich lipoproteins (TRL) can be taken up by macrophages, leading to the formation of foam cells, probably via receptor-mediated pathways. The present study was conducted to investigate whether the postprandial time point at which TRL are collected modulates this process. A meal containing refined olive oil was given to nine healthy young men and TRL were isolated from their serum at 2, 4 and 6 h postprandially.

High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2α concentrations relative to a control high-oleic acid meal: a randomized controlled trial.

Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear.

Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high-oleic acid meals; the secondary objective was to characterize the effects of linoleic acid-enriched high-fat meals relative to the control meal.

Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high-oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high-linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35-70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.

Myosin VI and Associated Proteins Are Expressed in Human Macrophages but Do Not Play a Role in Foam Cell Formation in THP-1 Cells.

Myosin VI (Myo6) functions in endocytosis in conjunction with binding partners including adaptor protein (AP)-2, disabled 2 (Dab2), and GAIP interacting protein C terminus 1 (GIPC1). This study aimed to investigate the expression and function of Myo6 in macrophages and its possible role in the endocytosis of lipoproteins during the induction of foam cell formation. Expression of Myo6, AP-2 ( α 2 subunit), and Dab2 in THP-1 macrophages and primary human monocyte-derived macrophages was demonstrated at the mRNA and protein level, but GIPC1 was only detected at the mRNA level.

Postprandial lipoproteins and the molecular regulation of vascular homeostasis.

Blood levels of triglyceride-rich lipoproteins (TRL) increase postprandially, and a delay in their clearance results in postprandial hyperlipidemia, an important risk factor in atherosclerosis development. Atherosclerosis is a multifactorial inflammatory disease, and its initiation involves endothelial dysfunction, invasion of the artery wall by leukocytes and subsequent formation of foam cells. TRL are implicated in several of these inflammatory processes, including the formation of damaging free radicals, leukocyte activation, endothelial dysfunction and foam cell formation.

Postprandial human triglyceride-rich lipoproteins increase chemoattractant protein secretion in human macrophages.

This study tested the hypothesis that postprandial triglyceride-rich lipoproteins (ppTGRL) have inflammatory effects in primary human monocyte-derived macrophages (HMDM). ppTGRL were isolated from normolipidemic human volunteers, and the production of chemokines and of inflammatory prostaglandins and leukotrienes via the arachidonic acid cascade in HMDM was determined, and their effect on monocyte chemotaxis were assessed. In addition, the possible role of extracellular lipases in the inflammatory effects of ppTGRL was evaluated.

Role of macrophage activation in the lipid metabolism of postprandial triacylglycerol-rich lipoproteins.

The potential link between the inflammatory effects of postprandial lipemia and the induction of macrophage foam cell formation by triacylglycerol-rich lipoproteins (TGRL) was studied using postprandial triacylglycerol-rich lipoproteins (ppTGRL) derived from human volunteers and primary human monocyte-derived macrophages (HMDM). Subjects were fed a test meal high in dairy fat, followed three hours later by isolation of serum ppTGRL. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes were induced in HMDM by treatment with lipopolysaccharide (LPS) or dexamethasone (DEX), respectively.

Coenzyme Q metabolism is disturbed in high fat diet-induced non-alcoholic fatty liver disease in rats.

Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks.

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.

The oxidative state of chylomicron remnants influences their modulation of human monocyte activation.

Chylomicron remnants (CMRs) contribute directly to human monocyte activation in vitro, by increasing reactive oxygen species (ROS) production and cell migration. In this study, the effects of the oxidative state of CMR on the degree of monocyte activation was investigated. CMR-like particles (CRLPs) were prepared in three different oxidative states, normal (CRLPs), protected from oxidation by incorporation of the antioxidant, probucol (pCRLPs), or oxidised with CuSO(4) (oxCRLPs).

Inhibition of macrophage inflammatory cytokine secretion by chylomicron remnants is dependent on their uptake by the low density lipoprotein receptor.

Secretion of pro-inflammatory chemokines and cytokines by macrophages is a contributory factor in the pathogenesis of atherosclerosis. In this study, the effects of chylomicron remnants (CMR), the lipoproteins which transport dietary fat in the blood, on the production of pro-inflammatory chemokine and cytokine secretion by macrophages was investigated using CMR-like particles (CRLPs) together with THP-1 macrophages or primary human macrophages (HMDM). Incubation of CRLPs or oxidized CRLPs (oxCRLPs) with HMDM or THP-1 macrophages for up to 24h led to a marked decrease in the secretion of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and the pro-inflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β (-50-90%), but these effects were reduced or abolished when CRLPs protected from oxidation by incorporation of the antioxidant drug, probucol, (pCRLPs) were used.

Endothelial cells as targets for chylomicron remnants.

Endothelial dysfunction is characterised by pro-inflammatory/pro-coagulant changes in the endothelium and supports leukocyte adhesion and transmigration, key steps in early atherogenesis. There is emerging evidence that triacylglycerol-rich lipoproteins (TGRLs) present in the circulation during the postprandial phase influence vascular inflammation but the specific contribution of the remnant lipoprotein component of TGRLs is largely unexplored and the mechanistic basis of their actions poorly defined. This article provides a brief overview of the evidence supporting direct actions of these particles on endothelial cells and highlights the importance of their fatty acid composition and oxidative state as determinants of their cellular actions.

Suppression of nuclear factor-kappaB activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles.

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated. In this study, the influence of CMR on the activity of NF-kappaB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP-1 and CMR-like particles (CRLPs).

Suppression of VLDL secretion by cultured hepatocytes incubated with chylomicron remnants enriched in n-3 polyunsaturated fatty acids is regulated by hepatic nuclear factor-4alpha.

Dietary n-3 polyunsaturated fatty acids (PUFA) suppress the secretion of very low density lipoprotein (VLDL) directly when delivered to the liver in chylomicron remnants (CMR). The role of sterol regulatory element-binding proteins (SREBPs) and hepatic nuclear factor-4alpha (HNF-4alpha) in the regulation of this effect was investigated. Chylomicron remnant-like particles (CRLPs) containing triacylglycerol (TG) from palm (rich in saturated fatty acids (SFA)) or fish (rich in n-3 PUFA) oil were incubated with cultured rat hepatocytes (24h) and the expression of protein and mRNA for SREBP-1, SREBP-2 and HNF-4alpha, and levels of mRNA for their target genes were determined.

Hepatic VLDL assembly is disturbed in a rat model of nonalcoholic fatty liver disease: is there a role for dietary coenzyme Q?

The overproduction of very-low-density lipoprotein (VLDL) is a characteristic feature of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to use a high-fat diet-induced model of NAFLD in rats to investigate 1) the influence of the disease on hepatic VLDL processing in the endoplasmic reticulum and 2) the potential modulatory effects of dietary coenzyme Q (CoQ). Rats were fed a standard low-fat diet (control) or a diet containing 35% fat (57% metabolizable energy).

Induction of non-alcoholic fatty liver disease and insulin resistance by feeding a high-fat diet in rats: does coenzyme Q monomethyl ether have a modulatory effect?

Objective: The aim of this study was to investigate the development of non-alcoholic fatty liver disease (NAFLD) in response to a high-fat diet in rats and to test the hypothesis that dietary coenzyme Q monomethyl ether (CoQme) has antisteatogenic effects.

Methods: Rats were fed a standard low-fat diet (control) for 18 wk or a diet containing 35% fat (57% metabolizable energy) for 10 wk, then divided into three groups for the following 8 wk. One group was given CoQ9me (30mg/kg body weight per day in 0.

Differential influence of different dietary fatty acids on very low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants.

The influence of dietary fats carried in chylomicron remnants on the hepatic secretion of very low-density lipoprotein (VLDL) was investigated using chylomicron remnant-like particles (CRLPs) and cultured rat hepatocytes as the experimental model. Chylomicron remnant-like particles containing triacylglycerol (TG) from palm, olive, or corn (enriched in saturated, monounsaturated, or n-6 polyunsaturated fatty acids) oil, respectively, were incubated with cultured hepatocytes for 5 hours. The medium was then removed and replaced with medium without CRLPs; and the secretion of TG, cholesterol, and apolipoprotein B48 during the following 16 hours was determined.

Oxidation of chylomicron remnants and vascular dysfunction.

Recent evidence suggests that chylomicron remnants (CMRs), the lipoproteins which carry dietary lipids in the blood, may play a direct role in the initiation of atherosclerosis by influencing vascular function. Unlike low-density lipoprotein (LDL), CMR do not require prior oxidation to bring about potentially pro-atherogenic effects on vascular endothelial cell function and macrophage foam cell formation. However, CMR carry oxidized lipids from the diet and may also become oxidized in the body, thus it is important to establish how the oxidative state of the particles may modulate these effects.

Effects of lycopene on the induction of foam cell formation by modified LDL.

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha] and anti-inflammatory (IL-10) cytokines was determined.

Differential modulation of hepatic very low-density lipoprotein secretion by triacylglycerol-rich lipoproteins derived from different oleic-acid rich dietary oils.

Minor components from dietary oils can modulate the atherogenic response of the TAG-rich lipoproteins (TRL) in which they are transported. In the present study we investigated the influence of TRL isolated from man after the intake of oleic acid-rich oils with different minor component compositions on VLDL secretion by rat primary hepatocytes. TRL were isolated from nine men after the intake of meals enriched with high-oleic sunflower oil (HOSO) or virgin olive oil (VOO) or VOO enriched with minor components (EVO).