- Cholesterol and Lipid Metabolism
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipoproteins and Cardiovascular Health
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Lipid metabolism and disorders
- Renal Transplantation Outcomes and Treatments
- Diet and metabolism studies
- Birth, Development, and Health
- Liver Disease and Transplantation
- Diet, Metabolism, and Disease
- Metabolism and Genetic Disorders
- Organ Transplantation Techniques and Outcomes
- Dialysis and Renal Disease Management
- Hormonal Regulation and Hypertension
- Adipose Tissue and Metabolism
- Ovarian function and disorders
- Paraoxonase enzyme and polymorphisms
- Diabetes Treatment and Management
- Gut microbiota and health
- Pancreatitis Pathology and Treatment
Karolinska Institutet
2016-2025
Karolinska University Hospital
2016-2025
RELX Group (United States)
2023
University of Groningen
2012-2021
University Medical Center Groningen
2012-2021
Center for Digestive and Liver Diseases
2006-2019
Simon Fraser University
2017
University of Amsterdam
2017
National University of Singapore
2017
TiFN
2010-2016
HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. binding to scavenger receptor-BI has been shown activate eNOS, although responsible entities and signaling pathways have remained enigmatic. Here we show that stimulates NO release in human endothelial cells induces vasodilation isolated aortae via intracellular Ca2+ mobilization Akt-mediated eNOS phosphorylation. The vasoactive effects of could be mimicked by three lysophospholipids present...
HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. binding to scavenger receptor-BI has been shown activate eNOS, although responsible entities and signaling pathways have remained enigmatic. Here we show that stimulates NO release in human endothelial cells induces vasodilation isolated aortae via intracellular Ca2+ mobilization Akt-mediated eNOS phosphorylation. The vasoactive effects of could be mimicked by three lysophospholipids present...
The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first events the general population.HDL was determined as its ability to suppress TNFα (tumor necrosis factor α)-induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression endothelial cells vitro (results expressed achieved percent reduction by individual related...
Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis perpetuate atherosclerotic plaque development. Mediators inflammation, ie, interleukin (IL)-6, elevated in patients with acute coronary syndromes may contribute to the exacerbation atherosclerosis.To assess role IL-6 atherosclerosis, ApoE-/--IL-6-/- double-knockout mice were generated, fed a normal chow diet, housed for 53+/-4 weeks. Mortality blood pressure unaltered. However, serum cholesterol levels subsequent...
Objective— Transsignaling of interleukin (IL)-6 is a central pathway in the pathogenesis disorders associated with chronic inflammation, such as Crohn disease, rheumatoid arthritis, and inflammatory colon cancer. Notably, IL-6 also represents an independent risk factor for coronary artery disease (CAD) humans crucially involved vascular processes. Methods Results— In present study, we showed that treatment fusion protein natural transsignaling inhibitor soluble glycoprotein 130 (sgp130)...
Recent studies have indicated that direct intestinal secretion of plasma cholesterol significantly contributes to fecal neutral sterol loss in mice. The physiological relevance this novel route, which represents a part the reverse transport pathway, has not been directly established vivo as yet. We developed method quantify fractional and absolute contributions several fluxes total mice, by assessing kinetics orally intravenously administered stable isotopically labeled combined with an...
High-density lipoprotein (HDL) levels are inversely proportional to the risk of atherosclerosis, but mechanisms HDL atheroprotection remain unclear. Monocyte chemoatractant protein-1 (MCP-1) constitutes an early component inflammatory response in atherosclerosis. Here we investigated influence on MCP-1 production vascular smooth muscle cells (VSMCs) and rat aortic explants.HDL inhibited thrombin-induced a concentration-dependent manner. The HDL-dependent inhibition was accompanied by...
High-fat diets promote hepatic lipid accumulation. Paradoxically, these also induce lipogenic gene expression in rodent liver. Whether high of genes actually results an increased flux through the de novo pathway vivo has not been demonstrated.To interrogate this apparent paradox, we have quantified lipogenesis C57Bl/6J mice fed either chow, a high-fat or n-3 polyunsaturated fatty acid (PUFA)-enriched diet. A novel approach based on mass isotopomer distribution analysis (MIDA) following...
AimsHigh-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 an important pro-inflammatory cytokine in early atherogenesis. There evidence that HDL can lose its protective function during inflammatory disease. In patients with end-stage renal disease (ESRD), epidemiological studies documented the inverse correlation between HDL-cholesterol and cardiovascular risk lost. Many structural modifications leading reduced been...
Atherosclerosis is linked to inflammation. HDL protects against atherosclerotic cardiovascular disease, mainly by mediating cholesterol efflux and reverse transport (RCT). The present study aimed test the impact of acute inflammation as well selected phase proteins on RCT with a macrophage-to-feces in vivo assay using intraperitoneal administration [(3)H]cholesterol-labeled macrophage foam cells. In patients sepsis, toward plasma were significantly decreased (P < 0.001). mice, (75...
Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme cholesterol synthesis. reduce plasma levels, but whether this is actually caused by inhibition de novo synthesis has not been clearly established. Using three different statins, we investigated effects on metabolism in mice detail. Surprisingly, direct measurement whole body revealed that was robustly increased statin-treated mice. Measurement organ-specific demonstrated liver predominantly responsible for...
Focus is shifting from HDL-C (high-density lipoprotein cholesterol) as predictive biomarker for cardiovascular disease (CVD) towards antiatherogenic HDL functionalities. Still, limited data exist on the prospective association of function metrics with CVD events. The current work aimed to determine, if baseline efflux capacity (CEC) associated future events in general population. Approach and Results: We performed a study among participants PREVEND (Prevention Renal Vascular End-stage...
Functional properties of high density lipoproteins (HDL) are increasingly recognized to play a physiological role in atheroprotection. Type 2 diabetes mellitus (T2DM) is characterized by low HDL cholesterol, but the effect chronic hyperglycemia on anti-inflammatory capacity HDL, metric function, unclear. Therefore, aim present study was establish impact T2DM capacity, taking paraoxonase-1 (PON-1) activity and grade inflammation into account.The determined as ability suppress tumor necrosis...
Plasma levels of high density lipoprotein (HDL) cholesterol and its major protein component apolipoprotein (apo) A-I are significantly reduced in both acute chronic inflammatory conditions, but the basis for this phenomenon is not well understood. We hypothesized that secretory phospholipase A<sub>2</sub>(sPLA<sub>2</sub>), an phase has been found association with HDL, promotes HDL catabolism. A series metabolic studies were performed transgenic mice specifically overexpress human...
The microsomal triglyceride transfer protein (MTP) is essential for the hepatic secretion of apolipoprotein (apo) B-containing lipoproteins. Previous studies have indicated that inhibition MTP results in decreased apoB plasma levels and secretion. However, metabolic effects overexpression not been investigated. We constructed a recombinant adenovirus expressing (AdhMTP) used it to assess mice. Injection AdhMTP into C57BL/6 mice resulted 3-fold increase activity compared injected with Adnull....
Adiponectin is a novel adipocytokine negatively correlated with parameters of the metabolic syndrome, such as body mass index (BMI), fat (BFM), and circulating insulin levels. Furthermore, actions directly on liver have been described. The aim present study was to characterize adiponectin levels, hepatic turnover, association key well systemic metabolism in cirrhosis, catabolic disease. Circulating levels turnover were investigated 20 patients advanced cirrhosis. Hepatic hemodynamics [portal...
Factors that regulate the metabolism of HDL and apolipoprotein A-I (apoA-I) are incompletely understood. Overexpression endothelial lipase (EL) markedly reduces plasma levels cholesterol apoA-I in mice, but mechanisms this effect remain unknown.We used different doses a recombinant adenoviral vector to overexpress human EL mice studied effects on phospholipase activity, lipids, particle size, turnover, tissue sites degradation mice. was associated with significant dose-dependent increase...
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 from peripheral cells its subsequent liver for further metabolism biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y13 (purinergic receptor P2Y, G protein–coupled, 13) activation essential HDL uptake but potential as a target RCT has not been documented. Here, we show...