A5048115388- Cardiac Fibrosis and Remodeling
- Viral Infections and Immunology Research
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- Tissue Engineering and Regenerative Medicine
- Bone and Dental Protein Studies
- Cardiovascular Function and Risk Factors
- S100 Proteins and Annexins
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Atherosclerosis and Cardiovascular Diseases
- Signaling Pathways in Disease
- Transplantation: Methods and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA regulation and disease
- Cardiac Valve Diseases and Treatments
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Whipple's Disease and Interleukins
- RNA Interference and Gene Delivery
- Cytomegalovirus and herpesvirus research
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
KU Leuven
2013-2023
Maastricht University
2012-2022
VIB-KU Leuven Center for Cancer Biology
2018-2021
Onze Lieve Vrouwziekenhuis Hospital
2017
Amsterdam University Medical Centers
2017
Netherlands Heart Institute
2013
Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal myocyte signaling pathways, growing evidence suggests inflammatory pathways as therapeutically targetable contributors to this process. We recently reported that microRNA-155 is a key mediator of cardiac inflammation injury in infectious myocarditis. Here, we investigated the impact manipulation hypertensive disease.Genetic loss or...
Regulation of RAS by ubiquitination The protein LZTR1 is mutated in human cancers and developmental diseases. Work from two groups now converges to implicate the regulating signaling small guanosine triphosphatase RAS. Steklov et al. showed that mice haploinsufficient for recapitulated aspects disease Noonan syndrome. Their biochemical studies associated with appears function as an adaptor promotes RAS, thus inhibiting its functions. Bigenzahn found a screen proteins whose absence led...
Viral myocarditis results from an adverse immune response to cardiotropic viruses, which causes irreversible myocyte destruction and heart failure in previously healthy people. The involvement of microRNAs their usefulness as therapeutic targets this process are unknown.To identify involved viral pathogenesis susceptibility.Cardiac were profiled both human Coxsackievirus B3-injected mice, comparing myocarditis-susceptible with nonsusceptible mouse strains longitudinally. MicroRNA responses...
Abstract Aims Viral myocarditis (VM) is an important cause of heart failure and sudden cardiac death in young healthy adults; it also aetiological precursor dilated cardiomyopathy. We explored the role miR-221/-222 family that up-regulated VM. Methods results Here, we show microRNA-221 (miR-221) miR-222 levels are significantly elevated during acute VM caused by Coxsackievirus B3 (CVB3). Both miRs expressed different cells infiltrating inflammatory cells, but their up-regulation upon mostly...
Rationale: To maintain cardiac mechanical and structural integrity after an ischemic insult, profound alterations occur within the extracellular matrix. Osteoglycin is a small leucine-rich proteoglycan previously described as marker of hypertrophy. Objective: establish whether osteoglycin may play role in function myocardial infarction (MI). Methods Results: expression associated with collagen deposition scar formation mouse human MI. Absence mice resulted significantly increased...
Optimal healing after myocardial infarction requires not only the induction of inflammation, but also its timely resolution. In patients, 30 days post infarction, circulating monocytes have increased expression Semaphorin3A (Sema3A) as compared to directly admission. This coincides with Cx3CR1—a marker non-classical that are important for immune resolution hence proper wound healing. mice, Sema3A increases in response ischemia being expressed by infiltrating leukocytes. Comparing...
Cardiovascular diseases remain the predominant cause of death worldwide, with prevalence heart failure continuing to increase. Despite increased knowledge metabolic alterations that occur in failure, novel therapies treat observed disturbances are still lacking.Mice were subjected pressure overload by means angiotensin-II infusion or transversal aortic constriction. MicroRNA-146a was either genetically pharmacologically knocked out overexpressed cardiomyocytes. Furthermore, overexpression...
Viral myocarditis (VM) is an inflammatory pathology of the myocardium triggered by a viral infection that may cause sudden death or heart failure (HF), especially in younger population. Current treatments only stabilize and improve cardiac function without resolving underlying cause. The factors induce VM to progress HF are still uncertain, but neutrophils have been increasingly associated with negative evolution pathologies. present study investigates contribution disease progression different ways.
Acute cellular rejection (ACR) is the adverse response of recipient's immune system against allogeneic graft. Using human surveillance endomyocardial biopsies (EMBs) manifesting ACR and murine grafts, we profiled implicated microRNAs (miRs) mRNAs. MiR profiling showed that miR-21, -142-3p, -142-5p, -146a, -146b, -155, -222, -223, -494 increased during in humans mice, whereas miR-149-5p decreased. mRNA revealed 70 common differentially regulated transcripts, all involved signaling...
Mice fully deficient in peptidylarginine deiminase 4 (PAD4) enzyme have preserved cardiac function and reduced collagen deposition during ageing. The cellular source of PAD4 is hypothesized to be neutrophils, likely due PAD4's involvement neutrophil extracellular trap release. We investigated haematopoietic impact on myocardial remodelling systemic inflammation ageing by generating mice with
Blood flow produces shear stress exerted on the endothelial layer of vessels. Spatial characterization proteome is required to uncover mechanisms activation by stress, as blood varies in vasculature. An integrative ubiquitinome and analysis shear-stressed cells demonstrated that non-degradative ubiquitination several GTPases regulated mechano-signaling. reveals increased small GTPase RAP1 descending aorta, a region exposed laminar stress. The ubiquitin ligase WWP2 identified novel regulator...
Abstract Aims Microvascular dysfunction has been proposed to drive heart failure with preserved ejection fraction (HFpEF), but the initiating molecular and cellular events are largely unknown. Our objective was determine when microvascular alterations in HFpEF begin, how they contribute disease progression, pericyte plays a role herein. Methods results dysfunction, characterized by inflammatory activation, loss of junctional barrier function, altered pericyte–endothelial crosstalk, assessed...
MicroRNA-103/107 regulate systemic glucose metabolism and insulin sensitivity. For this reason, inhibitory strategies for these microRNAs are currently being tested in clinical trials. Given the high metabolic demands of heart abundant cardiac expression miR-103/107, we questioned whether antagomiR-mediated inhibition miR-103/107 C57BL/6J mice impacts on function. Notably, fractional shortening decreased after 6 weeks antagomiR-103 -107 treatment. This was paralleled by a prolonged systolic...
Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. Osteoglycin (OGN) is part small leucine-rich repeat proteoglycan (SLRP) family. SLRP's may affect inflammatory and fibrotic processes, but implication OGN in cardiac inflammation resulting injury upon viral unknown.This study uncovered a previously unidentified 72-kDa variant that predominant human mouse samples myocarditis. Its absence mice significantly decreased Coxsackievirus-B3-induced...
Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause sudden cardiac death in young adults. Unfortunately, to date, pathological mechanisms underlying failure VM remain incompletely understood. In current study, we investigated if acute leads metabolic rewiring this process driven local inflammation. Transcriptomic analysis biopsies from patients a mouse model revealed prominent reductions expression multitude genes involved...
Myocardial damage as a consequence of cardiotropic viruses leads to broad variety clinical presentations and is still complicated condition diagnose treat. Whereas the extracellular matrix protein Secreted Protein Acidic Rich in Cysteine or SPARC has been implicated hypertensive ischemic heart disease by modulating collagen production cross-linking, its role cardiac inflammation endothelial function yet unknown. Absence mice resulted increased mortality, reduced systolic upon...
Secreted protein acidic and rich in cysteine (SPARC) is a non-structural extracellular matrix that regulates interactions between the neighboring cells. In cardiovascular system, it expressed by cardiac fibroblasts, endothelial cells, at lower levels ventricular cardiomyocytes. SPARC expression are increased upon myocardial injury also during hypertrophy fibrosis. We have previously shown improves function after infarction regulating post-synthetic procollagen processing, however whether...
Abstract Contractile myofiber units are mainly composed of thick myosin and thin actin (F-actin) filaments. F-Actin interacts with Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 2 (MICAL2). Indeed, MICAL2 modifies subunits promotes filament turnover by severing them preventing repolymerization. In this study, we found that increases during myogenic differentiation adult pluripotent stem cells (PSCs) towards skeletal, smooth cardiac muscle localizes in the nucleus...
Muscular dystrophies are debilitating neuromuscular disorders for which no cure exists. As this disorder affects both cardiac and skeletal muscle, patients would benefit from a cellular therapy that can simultaneously regenerate tissues. The current protocol to derive bipotent mesodermal progenitors differentiate into muscle relies on the spontaneous formation of embryoid bodies, thereby hampering further clinical translation. Additionally, as is largest organ in human body, high myogenic...
Viral myocarditis (VM) is severe cardiac inflammation that can result in sudden death or congestive heart failure previously healthy adults, with no effective therapy. Liver X receptor (LXR) agonists have both anti-inflammatory and lipid-lowering properties. This study investigates whether LXR agonist T0901317 may modulate viral replication during VM. (i) Adult mice were administered vehicle the onset of CVB3 virus (ii) treated 2 days prior to infection. Against what we expected, treatment...
Abstract Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal HFpEF-diseased obese ZSF1 rats by echocardiography. First, was confirmed pressure-volume loops compared lean control rats. In echocardiography,...
Pathological innate and adaptive immune response upon viral infection may lead to cardiac injury dysfunction. Stabilin-1 is a scavenger receptor that regulates several aspects of the immunity. Whether stabilin-1 affects inflammatory during myocarditis (VM) entirely unknown. Here, we assess role in pathogenesis VM its suitability as therapeutic target. Genetic loss increased mortality necrosis mouse model human Coxsackievirus B3 (CVB3)-induced myocarditis. Absence significantly reduced...