A5044870115- Blood Coagulation and Thrombosis Mechanisms
- Cancer, Lipids, and Metabolism
- Lipoproteins and Cardiovascular Health
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Venous Thromboembolism Diagnosis and Management
- Atherosclerosis and Cardiovascular Diseases
- Hemophilia Treatment and Research
- Nuclear Receptors and Signaling
- Platelet Disorders and Treatments
- Pharmacogenetics and Drug Metabolism
- Protease and Inhibitor Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- PI3K/AKT/mTOR signaling in cancer
- Cholesterol and Lipid Metabolism
- Immune cells in cancer
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- Animal Genetics and Reproduction
- Protein Degradation and Inhibitors
- Coronary Interventions and Diagnostics
- Cell Adhesion Molecules Research
- Blood properties and coagulation
Leiden University Medical Center
2016-2025
Centre for Human Drug Research
1999-2017
Leiden University
1997-2017
Amsterdam UMC Location University of Amsterdam
2005-2017
Maastricht University
2017
Utrecht University
2003-2014
Kanazawa University
2014
The Netherlands Cancer Institute
2014
Netherlands Organisation for Applied Scientific Research
2000-2008
The University of Texas Southwestern Medical Center
1999-2006
Background — The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and sensitivity to p53-induced cell death smooth muscle cells isolated from these have fueled speculation about role lesion destabilization plaque rupture. In this study, we describe a strategy promote (thrombotic) rupture preexisting lesions using remodeling. Methods Results Carotid atherogenesis was initiated apolipoprotein E knockout mice by placement perivascular silastic collar. resulting were...
Cell proliferation and cell death (either necrosis or apoptosis) are key processes in the progression of atherosclerosis. The tumor suppressor gene p53 is an essential upregulated human atherosclerotic plaques, both smooth muscle cells macrophages. In present study, we investigated importance macrophage atherosclerosis using bone marrow transplantation APOE*3-Leiden transgenic mice, animal model for human-like mice were lethally irradiated reconstituted with derived from either p53-deficient...
Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In present study, we investigated effects of diet composition feeding period on serum cholesterol exposure amount atherosclerosis in aortic sinus these mice, using quantitative image analysis. On each three diets tested--a low-fat diet, a high-saturated-fat/cholesterol high...
The VLDL receptor (VLDLr) is involved in tissue delivery of VLDL-triglyceride (TG)-derived FFA by facilitating the expression lipoprotein lipase (LPL). However, vldlr-/- mice do not show altered plasma levels, despite reduced LPL expression. Because activity crucial postprandial lipid metabolism, we investigated whether VLDLr plays a role chylomicron clearance. Fed TG levels were 2.5-fold increased compared with those vldlr+/+ littermates (1.20 +/- 0.37 mM vs. 0.47 0.18 mM; P < 0.001)....
Elevated von Willebrand factor (VWF) levels correlate with higher risk of atherosclerosis-related arterial thrombosis (atherothrombosis). Silencing the VWF gene via small-interfering RNAs (siRNAs) could mitigate this risk. Previous studies successfully delivered siRNA to endothelium healthy, wild-type (WT) mice using lipid nanoparticles (LNPs). This study aimed investigate whether LNP-siRNA strategy achieve endothelium-specific Vwf-silencing under diseased conditions prolonged...
ABSTRACT Background Migraine increases the risk of ischemic stroke and white matter hyperintensities (WMH), especially in women. Underlying shared mechanisms may include endothelial activation hypercoagulability. We assessed these markers middle‐aged women with without migraine to explore their role WMH development. Methods cross‐sectionally measured fibrinogen von Willebrand factor antigen (VWF:Ag) levels as activation, (F)IX FXI activity (FXI:C) hypercoagulability four groups aged 40–60...
Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well inflammation, a pivotal factor restenosis. TNFalpha, key regulator of inflammatory responses, may exert critical influence on development restenosis PCI. The GENetic DEterminants Restenosis (GENDER) project included 3104 patients who underwent successful Systematic genotyping for six polymorphisms TNFalpha gene was performed. role also assessed ApoE*3-Leiden mice, knockout...
Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists genetic important in the restenotic process as well inflammation, pivotal factor restenosis. Association studies have identified genes may predispose to restenosis, but confirmation by large prospective lacking. Our aim was identify polymorphisms and haplotypes involved inflammatory pathways restenosis.The GENetic...
In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. present study, we investigated vivo role of macrophage specific LRP atherogenesis independent its uptake lipoproteins.We generated macrophage-specific LRP-deficient mice on an apoE/LDLR double-deficient background. Macrophage deletion did not affect plasma cholesterol and triglyceride levels, distribution, blood monocyte counts. Nevertheless,...
Abstract Background Cushing’s syndrome (CS) is associated with an hypercoagulable state and increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients CS are currently lacking. We aimed to map the current clinical practice for management across reference centers (RCs) European Reference Network Rare Endocrine Conditions (Endo-ERN), which endorsed specifically diagnosis treatment CS. Using EU survey tool, a primary screening survey,...