A5022091149- Nuclear Receptors and Signaling
- Macrophage Migration Inhibitory Factor
- Protease and Inhibitor Mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Galectins and Cancer Biology
- Signaling Pathways in Disease
- Coronary Interventions and Diagnostics
- Kruppel-like factors research
- Circular RNAs in diseases
- Aortic aneurysm repair treatments
- TGF-β signaling in diseases
- Apelin-related biomedical research
- Cardiomyopathy and Myosin Studies
- Blood Coagulation and Thrombosis Mechanisms
- Connective tissue disorders research
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
- Cardiac Fibrosis and Remodeling
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Angiogenesis and VEGF in Cancer
- Platelet Disorders and Treatments
- Cancer-related gene regulation
- Bone Metabolism and Diseases
University of Amsterdam
2015-2024
Amsterdam University Medical Centers
2018-2024
Amsterdam UMC Location University of Amsterdam
2012-2021
Ludwig-Maximilians-Universität München
2016
Sanquin
2013
Maastricht University
2003-2011
Leiden University Medical Center
2007-2010
Erasmus MC
2010
University Medical Center
2010
Leiden University
2010
The alarmin S100A9 has been identified as a potential therapeutic target in myocardial infarction. Short-term blockade during the inflammatory phase post-myocardial infarction inhibits systemic and cardiac inflammation improves function long term.To evaluate impact of on postischemic repair.We assessed function, hematopoietic response, myeloid phagocyte dynamics WT (wild type) C57BL/6 mice with permanent coronary artery ligation, treated specific blocker ABR-238901 for 7 or 21 days. In...
Atherosclerosis is initiated by the infiltration of monocytes into subendothelial space vessel wall and subsequent lipid accumulation activated macrophages. The molecular mechanisms involved in anomalous behavior macrophages atherogenesis have only partially been disclosed. Chitotriosidase human cartilage gp-39 (HC gp-39) are members chitinase family proteins expressed lipid-laden accumulated various organs during Gaucher disease. In addition, as shown this study, chitotriosidase HC can be...
Atherosclerosis is an inflammatory disease in which macrophage activation and lipid loading play a crucial role. In this study, we investigated expression function of the NR4A nuclear receptor family, comprising Nur77 (NR4A1, TR3), Nurr1 (NR4A2), NOR-1 (NR4A3) human macrophages.Nur77, Nurr1, are expressed early advanced atherosclerotic lesion macrophages primarily areas plaque activation/progression as detected by situ-hybridization immunohistochemistry. Protein localizes to nucleus. Primary...
Nuclear receptor Nur77, also known as NR4A1, TR3, or NGFI-B, is expressed in human atherosclerotic lesions macrophages, endothelial cells, T cells and smooth muscle cells. Macrophages play a critical role atherosclerosis the function of Nur77 lesion macrophages has not yet been investigated.This study aims to delineate assess effect bone marrow-specific deficiency on atherosclerosis.We investigated macrophage polarization using marrow-derived (BMM) from wild-type Nur77-knockout (Nur77(-/-))...
Von Willebrand Factor (vWF) mRNA was identified in fractionated polyA+ RNA preparations isolated from cultured human endothelial cells. Micro-injection of specific fractions Xenopus laevis oocytes provoked the synthesis a vWF-like product which could be detected with an immunoradiometric assay relying on Sepharose-linked monoclonal anti-vWF IgG and different radiolabeled IgGs. A vWF-mRNA-containing preparation served as substrate for size-selected cDNA-expression library 60 000 colonies...
Activation of macrophages by inflammatory stimuli induces reprogramming mitochondrial metabolism to support the production pro-inflammatory cytokines and nitric oxide. Hallmarks this metabolic rewiring are downregulation α-ketoglutarate formation isocitrate dehydrogenase (IDH) accumulation glutamine-derived succinate, which enhances response via activity succinate (SDH). Here, we identify nuclear receptor Nur77 (Nr4a1) as a key upstream transcriptional regulator switch in macrophages....
Bile acids are established signaling molecules next to their role in the intestinal emulsification and uptake of lipids. We here aimed identify a potential interaction between bile CD4+ Th cells, which central adaptive immune responses. screened distinct acid species for potency affect T cell function. Primary human mouse cells as well Jurkat were used gain insight into mechanism underlying these effects. found that unconjugated lithocholic (LCA) impedes Th1 activation measured by i)...
Chronic vascular inflammation is driven by interactions between activated leukocytes and the endothelium. Leukocyte β2-integrins bind to endothelial ICAM-1 (InterCellular Adhesion Molecule-1), which allows leukocyte spreading, crawling transendothelial migration. Leukocytes scan endothelium for permissive sites transmigrate suggestive apical membrane heterogeneity within However, molecular basis this unknown. adhesion induces clustering promotes its association actin-binding proteins...
Smooth muscle cells (SMCs) play a key role in intimal thickening atherosclerosis and restenosis. The precise signaling pathways by which the proliferation of SMCs is regulated are largely unknown. TR3 orphan receptor, mitogen-induced nuclear receptor (MINOR), T (NOT) subfamily transcription factors belonging to superfamily induced activated SMCs. In this study, we investigated these SMC atherogenesis.Multiple human vascular specimens at distinct stages (lesion types II V American Heart...
3beta-Hydroxysteroid dehydrogenase type 2 (HSD3B2) is a steroid-metabolizing enzyme that essential for adrenal production of mineralocorticoids and glucocorticoids. Thus, HSD3B2 expressed at high levels in the glomerulosa fasciculata, where these steroids are produced. In contrast, dehydroepiandrosterone (DHEA) DHEA sulfate reticularis inversely correlated with expression HSD3B2. The reasons zonal not known but represent an important aspect biochemical zonation adrenal. Using microarray,...
Chronic changes in blood flow induce an adaptation of vascular caliber. Thus, arteries show inward remodeling after a reduction flow. We hypothesized that this depends on the crosslinking enzyme tissue-type transglutaminase (tTG). Flow-dependent was studied wild-type (WT) and tTG-null mice using surgically imposed change small mesenteric arteries. WT showed 2 days low flow, which absent from mice. Yet, continued for 7 days, similar Studying alternative pathways remodeling, we identified...
The energetic costs of behavioral chronic stress are unlikely to be sustainable without neuronal plasticity. Mitochondria have the capacity handle synaptic activity up a limit before depletion occurs. Protective mechanisms driven by induction genes likely evolved buffer consequences on excitatory neurons in prefrontal cortex (PFC), as this circuitry is vulnerable excitotoxic insults. Little known about involved mitochondrial adaptation buildup stress. Using combinations genetic manipulations...
AimsAltered blood flow affects vascular tone, attracts inflammatory cells, and leads to microvascular remodelling. We tested the hypothesis that inflammation facilitates remodelling response, but tone determines its direction (inward or outward).
Purpose of review To understand chronic inflammatory diseases such as atherosclerosis, we require in-depth knowledge on immune-cell differentiation, function specific subsets and endothelial cell-mediated extravasation. In this review, summarize a number very recent observations the pivotal NR4A nuclear receptors in immunity atherosclerosis. Recent findings are involved negative selection thymocytes, Treg differentiation development Ly6C- monocytes. Nur77 Nurr1 attenuate atherosclerosis mice...
Nuclear receptor Nur77, also referred to as NR4A1 or TR3, plays an important role in innate and adaptive immunity. Nur77 is crucial regulating the T helper 1/regulatory T-cell balance, expressed macrophages drives M2 macrophage polarization. In this study we aimed define function of inflammatory bowel disease. wild-type Nur77-/- mice, colitis development was studied dextran sodium sulphate (DSS)- 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced models. To understand underlying mechanism,...
Abstract Allergic asthma is characterized by persistent chronic airway inflammation, which leads to mucus hypersecretion and hyperresponsiveness. Nuclear receptor Nur77 plays a pivotal role in distinct immune inflammatory cells expressed eosinophils lung epithelium. However, the of allergic inflammation has not been studied so far. In present study, we determined using murine model OVA-induced inflammation. We found that OVA-challenged knockout (KO) mice show significantly enhanced...
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure-lowering drugs used to reduce events; however, this not sufficient for most patients. In aorta smooth muscle cell-specific sirtuin-1-deficient mice, spontaneous senescence observed. Resveratrol known enhance sirtuin-1 activity senescence, which prompted us investigate effectiveness resveratrol...