A5084509185- Atherosclerosis and Cardiovascular Diseases
- Cardiac Fibrosis and Remodeling
- Chemokine receptors and signaling
- Cardiac Ischemia and Reperfusion
- Adipokines, Inflammation, and Metabolic Diseases
- Cell Adhesion Molecules Research
- Mast cells and histamine
- GDF15 and Related Biomarkers
- Extracellular vesicles in disease
- Sperm and Testicular Function
- Immune cells in cancer
- Nutrition and Health in Aging
- Cardiovascular Function and Risk Factors
- Reproductive Biology and Fertility
- Mechanical Circulatory Support Devices
- Cardiovascular Disease and Adiposity
- RNA Interference and Gene Delivery
- Protease and Inhibitor Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immune Response and Inflammation
- Inflammatory Biomarkers in Disease Prognosis
- Inflammasome and immune disorders
- MicroRNA in disease regulation
University Medical Center Utrecht
2016-2025
Utrecht University
2016-2025
Centre for Human Drug Research
2011-2024
Leiden University
2011-2024
Heidelberg University
1985-2024
University Hospital Heidelberg
2013-2024
University College London
2017
Netherlands Heart Institute
2017
University of Manchester
2017
Manchester Academic Health Science Centre
2017
Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within cells of human plaques has not been fully assessed. Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding pathophysiology underlying atherosclerosis. We performed RNA ATAC sequencing on carotid atherosclerotic to define at play determine transcriptomic epigenomic characteristics. identified 14 distinct cell populations including endothelial cells,...
Myocardial infarction (MI) triggers an intense inflammatory response that is associated with infarct expansion and detrimental for cardiac function. Interleukin (IL)-1β IL-18 are key players in this controlled by the NLRP3-inflammasome. In current study, we therefore hypothesized selective inhibition of NLRP3-inflammasome reduces size preserves function a porcine MI model.Thirty female landrace pigs were subjected to 75 min transluminal balloon occlusion treated inhibitor MCC950 (6 or 3...
Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection RNA panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based early- and late-stage non-small-cell lung cancer 518 validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92–0.96; p < 0.001; n 106...
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets involved in cancer progression and considered a promising biosource detection, as they alter their RNA content upon local systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the of 18 types. With 99% specificity asymptomatic controls, thromboSeq correctly detected presence two-thirds 1,096 samples stage I–IV half 352 I–III...
The loss-of-function of the proprotein convertase subtilisin-kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low-density lipoprotein cholesterol (LDL-C) levels. Both CRISPR/Cas9 and CRISPR-based editor-mediated Pcsk9 inactivation have successfully lowered LDL-C PCSK9 levels preclinical models. Despite promising results, these studies did not report how vehicle-mediated CRISPR delivery inactivating affected receptor recycling vitro or ex vivo....
Background— Mast cells are major effector in allergy and host defense responses. Their increased number state of activation perivascular tissue during atherosclerosis may point to a role cardiovascular disorders. In the present study, we investigated contribution mast atherogenesis plaque stability apolipoprotein E–deficient mice. Methods Results— We show here that episodes systemic cell progression mice leads robust expansion. Targeted advanced plaques sharply increases incidence...
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...
Background and Purpose The aetiology of inflammation in the liver vessel wall, leading to non‐alcoholic steatohepatitis ( NASH ) atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important tackle inflammatory status. Exendin‐4, a glucagon‐like peptide‐1 GLP‐1 receptor agonist, reduces hepatic steatosis has been suggested reduce atherosclerosis; however, its effects on are underexplored. Here, we...
Background— Recent studies found an immune regulatory role for Y chromosome and a relationship between loss of (LOY) in blood cells higher risk cancer mortality. Given involvement atherosclerosis, we hypothesized that LOY is associated with the severity atherosclerotic plaque characteristics outcome men undergoing carotid endarterectomy. Methods Results— was quantified from raw intensity genotyping data within Athero-Express biobank study. Plaques were dissected, culprit lesions used...
Objective: To determine whether MCP-1 (monocyte chemoattractant protein 1) levels in human atherosclerotic plaques associate with plaque vulnerability features. Approach and Results: We measured samples from 1199 patients the Athero-EXPRESS Biobank who underwent endarterectomy for treatment of carotid stenosis. explored associations histopathologic molecular features vulnerability, clinical manifestations, vascular events up to 3 years after endarterectomy. Following adjustments age, sex,...
Lipid Nanoparticles (LNPs) are a promising drug delivery vehicle for clinical siRNA delivery. Modified mRNA (modRNA) has recently gained great attention as therapeutic molecule in cardiac regeneration. However, to be functional, it must first reach the diseased myocardium, enter target cell, escape from endosomal compartment into cytosol and translated functional protein. is unknown if LNPs can effectively deliver mRNA, which much larger than siRNA, ischemic myocardium. Here, we evaluated...
Fibrosis is a major cause of mortality worldwide, characterized by myofibroblast activation and excessive extracellular matrix deposition. Systemic sclerosis prototypic fibrotic disease in which CXCL4 increased strongly correlates with skin lung fibrosis. Here we aim to elucidate the role fibrosis development. levels are multiple inflammatory mouse models, and, using CXCL4-deficient mice, demonstrate essential promoting events skin, lungs, heart. Overexpressing human mice aggravates, whereas...
Extracellular vesicles (EVs) have emerged as biocompatible drug delivery vehicles due to their native ability deliver bioactive cargo recipient cells. However, the application of EVs a therapeutic vehicle is hampered by effective methods for endogenously loading target proteins inside and unloading after Most EV-based engineered limited efficiency owing inefficient endosomal escape or release from intraluminal attachment EV membrane. Here, we describe 'Technology Of Protein through Vesicles'...
Despite research efforts being made towards preserving (or even regenerating) heart tissue after an ischemic event, there is a lack of resources in current clinical treatment modalities for patients with acute myocardial infarction that specifically address cardiac impairment. Modified messenger RNA (modRNA) presents compelling properties could allow new therapeutic strategies to tackle the underlying molecular pathways ultimately lead development chronic failure. However, application modRNA...
Abstract Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) constitute a promising therapy for myocardial infarction (MI). The lack of an effective immunosuppressive regimen, combined with single-cell transplantations, results in suboptimal outcomes, such as poor engraftment and compromised therapeutic efficacy. This study aimed to confirm the increased retention hiPSC-CMs microtissues (CMTs) over grafts. To ensure long-term survival CMTs potential cardiac applications,...
Chemokines play an important role in atherogenesis and ischemic injury repair; however, prospective data on individual chemokines unstable angina pectoris (UAP) are scarce. Therefore, we assessed chemokine patterns a cohort of patients with UAP.Plasma samples 54 Braunwald class IIIB UAP were examined at baseline for 11 5 inflammatory mediators via multiplex analysis. Levels CC ligand (CCL)-5 (also known as RANTES [regulated activation, normally T-cell expressed, secreted]; 32.7 versus 23.1...
The chemokine receptor CXCR3 is implicated in migration of leukocytes to sites inflammation. Antagonizing may be a strategy inhibit inflammation-induced leukocyte and subsequently reduce atherosclerosis. We used the specific antagonist NBI-74330 block CXCR3-mediated signaling peritonitis diet-induced atherosclerosis.Antagonizing with resulted significant reduction CD4+ T cell macrophage peritoneal cavity, which was as shown ex vivo studies totally dependent. Atherosclerotic lesion formation...
Objective— Despite common disbelief that neutrophils are involved in atherosclerosis, evidence is accumulating for a causal role of atherosclerosis. CC chemokine ligand (CCL)3 an inflammatory and its expression significantly increased during atherosclerotic lesion formation mice. It has recently been shown under conditions inflammation can migrate along CCL3 gradient. In this study, we aimed to elucidate the leukocyte-derived atherogenesis. Methods Results— Irradiated low density lipoprotein...