A5002187107- Aortic Disease and Treatment Approaches
- Connective tissue disorders research
- Aortic aneurysm repair treatments
- Nuclear Receptors and Signaling
- Cardiac Valve Diseases and Treatments
- Macrophage Migration Inhibitory Factor
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Atherosclerosis and Cardiovascular Diseases
- Cardiovascular Issues in Pregnancy
- Blood Coagulation and Thrombosis Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Cardiac Fibrosis and Remodeling
- Signaling Pathways in Disease
- Hormonal Regulation and Hypertension
- Platelet Disorders and Treatments
- Cellular Mechanics and Interactions
- Apelin-related biomedical research
- Angiogenesis and VEGF in Cancer
- Circular RNAs in diseases
- S100 Proteins and Annexins
- Hippo pathway signaling and YAP/TAZ
- Infectious Aortic and Vascular Conditions
- Congenital heart defects research
- Chemokine receptors and signaling
Amsterdam University Medical Centers
2018-2025
University of Amsterdam
2016-2025
Amsterdam UMC Location University of Amsterdam
2013-2023
University Medical Center Groningen
2015-2021
Leiden University Medical Center
2010-2021
Radboud University Nijmegen
2015-2021
Radboud University Medical Center
2021
Wolters Kluwer (Netherlands)
2012-2018
Ludwig-Maximilians-Universität München
2016
Netherlands Heart Institute
2015
Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by dilatation. Treatment losartan, angiotensin-II receptor-1 blocker, may reduce dilatation rate in patients. In this multicentre, open-label, randomized controlled trial blinded assessments, we compared losartan treatment no additional operated and unoperated adults syndrome. The primary endpoint was at any predefined level after 3 years follow-up, as determined magnetic resonance...
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...
The purpose of this study was to evaluate the effect combined deletion ABCA1 and ABCG1 expression in macrophages on foam cell formation atherosclerosis.LDL receptor knockout (KO) mice were transplanted with bone marrow from ABCA1/ABCG1 double KO (dKO) mice. Plasma cholesterol levels after 6 weeks Western-type diet (WTD) feeding significantly lower dKO than KO, control animals. Extreme present various tissues peritoneal cavity Furthermore, severe hypoplasia thymus a significant decrease...
Growth differentiation factor (GDF) 15 is a member of the transforming growth β (TGF-β) superfamily, which operates in acute phase responses through currently unknown receptor. Elevated GDF-15 serum levels were recently identified as risk for coronary syndromes. We show that expression up-regulated disease progresses murine atherosclerosis and primarily colocalizes with plaque macrophages. Hematopoietic deficiency low density lipoprotein receptor−/− mice led to impaired initial lesion...
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(-/-))...
It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates effectiveness genetically classified subgroups.In this predefined substudy of COMPARE, were randomized to daily receive 100 mg or no losartan. Aortic root dimensions measured by MRI at baseline and after 3 years. FBN1 mutations based on fibrillin-1 protein effect into (1) haploinsufficiency, decreased amount normal fibrillin-1,...
The aorta in Marfan syndrome (MFS) patients is variably affected. We investigated the assumed genotype-effect on protein production as a risk factor for severe aortic phenotype adult MFS patients.We collected clinical and genetic data from all 570 adults with who had been included Dutch CONgenital CORvitia registry since start 2001. Mean age was 36.5 ± 13.5 years (51.2% male, 28.9% prior surgery, 8.2% dissection). Patients were prospectively followed mean duration of 8.2 3.1 years. Men more...
BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1 . The aim of this cohort study to provide further insights into the natural history vEDS describe genotype-phenotype correlations Dutch multicenter optimize patient care increase awareness disease. METHODS: Individuals throughout Netherlands were included. phenotype was charted retrospective...
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...
Abstract Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture the major cause of death. MFS patients with an diameter below advised limit for prophylactic surgery (<5 cm) may unexpectedly experience dissection or rupture, despite yearly monitoring. Hence, there clear need improved prognostic markers to predict such events. We hypothesize that elastin fragments play causal role calcification MFS, and microcalcification serves as marker disease severity. To address...
The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no was found clinical endpoints, possibly due to short follow-up period. aim the current study therefore investigate long-term outcomes after treatment.In original (inclusion 2008-2009), adult patients MFS (n = 233) were randomly allocated either angiotensin-II receptor blocker losartan® top regular (β-blockers 71%...
Background Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution tissue inflammation not addressed so far. Methodology/Principal Findings Here we showed that both are up-regulated patients MFS. We analyzed transcriptome-wide gene expression 55 MFS using Affymetrix Human Exon 1.0 ST Array levels...
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...
Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which modified post-translationally glycosylation. This study aimed to characterize the glycoproteome of aortic ECM from patients with MFS and relate it aortopathy. Approach Results: extracts aneurysmal ascending tissue without were enriched for glycopeptides. Direct N-glycopeptide analysis mass spectrometry identified 141 glycoforms 47 glycosites within 35 glycoproteins human ECM....
Endothelial YAP/TAZ (YAP is also known as YAP1, and TAZ WWTR1) signaling crucial for sprouting angiogenesis vascular homeostasis. However, the underlying molecular mechanisms that explain how control vasculature remain unclear. This study reveals focal adhesion protein deleted-in-liver-cancer 1 (DLC1) a direct transcriptional target of activated YAP/TAZ-TEAD complex. We find substrate stiffening VEGF stimuli promote expression DLC1 in endothelial cells. In turn, levels are YAP dependent,...
BackgroundInflammatory bowel disease is characterized by chronic intestinal inflammation. Azathioprine and its metabolite 6-mercaptopurine (6-MP) are effective immunosuppressive drugs that widely used in patients with inflammatory disease. However, established understanding of their mechanism limited. 6-MP have been shown to affect small GTPase Rac1 T cells endothelial cells, whereas the effect on macrophages gut epithelial unknown.
Azathioprine and its metabolite 6-mercaptopurine (6-MP) are well established immunosuppressive drugs. Common understanding of their properties is largely limited to immune cells. However, in this study, the mechanism underlying protective role 6-MP endothelial cell activation investigated. Because derivative 6-thioguanosine-5'-triphosphate (6-T-GTP) were shown block GTPase Rac1 T lymphocytes, we focused on Rac1-mediated processes Indeed, 6-T-GTP decreased As a result, compounds inhibited...
Recently, we demonstrated that losartan reduced the aortic root dilatation rate (AoDR) in adults with Marfan syndrome (MFS); however, responsiveness was diverse. The aim to determine role of transforming growth factor-β (TGF-β) as therapeutic biomarker for effectiveness on AoDR.Baseline plasma TGF-β levels 22 healthy controls and 99 MFS patients, after 1 month treatment 42 patients were measured. AoDR assessed by magnetic resonance imaging at baseline 3 years follow-up.Patients had higher...