A5087169555- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Angiogenesis and VEGF in Cancer
- Cellular Mechanics and Interactions
- Platelet Disorders and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Protein Kinase Regulation and GTPase Signaling
- Chemokine receptors and signaling
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
- Photoreceptor and optogenetics research
- Immune Response and Inflammation
- Hippo pathway signaling and YAP/TAZ
- Caveolin-1 and cellular processes
- Immunotherapy and Immune Responses
- Receptor Mechanisms and Signaling
- Retinal Development and Disorders
- Wnt/β-catenin signaling in development and cancer
- Hematopoietic Stem Cell Transplantation
- Blood disorders and treatments
- Cytokine Signaling Pathways and Interactions
- Erythrocyte Function and Pathophysiology
- Monoclonal and Polyclonal Antibodies Research
- Blood properties and coagulation
- Nitric Oxide and Endothelin Effects
Sanquin
2016-2025
University of Amsterdam
2016-2025
Amsterdam University Medical Centers
2019-2025
Amsterdam UMC Location University of Amsterdam
2013-2024
The Netherlands Cancer Institute
2021-2023
Centre for Advanced Microscopy
2019-2021
Western University
2016
Radboud University Nijmegen
2016
Radboud University Medical Center
2016
University of Manitoba
2016
Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms responsible for its pathogenicity are poorly defined. Because Lp(a) prominent carrier of proinflammatory oxidized phospholipids (OxPLs), part atherothrombosis might be mediated through this pathway. In vivo imaging techniques including magnetic resonance imaging, (18)F-fluorodeoxyglucose uptake positron emission tomography/computed tomography and single-photon computed were...
Abstract Leukocyte transendothelial migration (TEM) has been modeled as a multistep process beginning with rolling adhesion, followed by firm and ending either transcellular or paracellular passage of the leukocyte across endothelial monolayer. In case TEM, cell (EC) junctions are transiently disassembled to allow leukocytes. Numerous lines evidence demonstrate that tyrosine phosphorylation adherens junction proteins, such vascular cadherin (VE-cadherin) β-catenin, correlates disassembly...
Reactive oxygen species (ROS) control the integrity of vascular endothelium. Our laboratory has recently shown that transduction human umbilical vein endothelial cells (HUVECs) with an active variant small GTPase Rac promotes production ROS, ROS-dependent activation p38 mitogen-activated protein kinase, and loss vascular/endothelial-cadherin-mediated cell-cell adhesion. Here we show HUVECs express mRNAs for NOX2 as well NOX4 mRNA, but not NOX1 or NOX3. Interestingly, was expressed at...
The integrity of the endothelium is dependent on cell-cell adhesion, which mediated by vascular-endothelial (VE)-cadherin. Proper VE-cadherin-mediated homotypic adhesion is, in turn, connection between VE-cadherin and cortical actin cytoskeleton. Rho-like small GTPases are key molecular switches that control cytoskeletal dynamics cadherin function epithelial as well endothelial cells. We show here a cell-penetrating, constitutively active form Rac (Tat-RacV12) induces rapid loss cells from...
Leukocyte adhesion is mediated totally and transendothelial migration partially by heterotypic interactions between the β 1 - 2 -integrins on leukocytes their ligands, Ig-like cell molecules (Ig-CAM), VCAM-1, ICAM-1, endothelium. Both integrins Ig-CAMs are known to have signaling capacities. In this study we analyzed role of VCAM-1-mediated in control endothelial cell-cell leukocyte migration. Antibody-mediated cross-linking VCAM-1 IL-1β-activated primary human umbilical vein cells (pHUVEC)...
Objective— The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results— found profound structural alterations in from mice type 1 depletion hematopoietic component fatty degeneration. Blood flow (fluorescent microspheres) density (immunohistochemistry) were remarkably reduced. Flow cytometry verified MECA-32 + endothelial cells. Cultured...
During trans-endothelial migration (TEM), leukocytes use adhesion receptors such as intercellular molecule-1 (ICAM1) to adhere the endothelium. In response this interaction, endothelium throws up dynamic membrane protrusions, forming a cup that partially surrounds adherent leukocyte. Little is known about signaling pathways regulate formation. study, we show RhoG activated downstream from ICAM1 engagement. This activation requires intracellular domain of ICAM1. colocalizes with and binds...
Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot interest as anti-hyperglycemic therapy type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties may behave immobilized anti-coagulant on endothelial cells. Here, we studied the expression activity human relation to prothrombogenic phenotype. Using...
Abstract During immune surveillance and inflammation, leukocytes exit the vasculature through transient openings in endothelium without causing plasma leakage. However, exact mechanisms behind this intriguing phenomenon are still unknown. Here we report that maintenance of endothelial barrier integrity during leukocyte diapedesis requires local RhoA cycling. Endothelial depletion vitro or Rho inhibition vivo provokes neutrophil-induced vascular leakage manifests physical movement neutrophils...
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...
Endothelial cell-cell junctions maintain a restrictive barrier that is tightly regulated to allow dynamic responses permeability-inducing angiogenic factors as well inflammatory agents and adherent leukocytes. The ability of these stimuli transiently remodel adherens (AJs) depends on Rho-GTPase-controlled cytoskeletal rearrangements. How activity Rho-GTPases spatio-temporally controlled at endothelial AJs by guanine-nucleotide exchange (GEFs) incompletely understood. Here, we identify...
The most successful genetically encoded calcium indicators (GECIs) employ an intensity or ratiometric readout. Despite a large calcium-dependent change in fluorescence intensity, the quantification of concentrations with GECIs is problematic, which further complicated by sensitivity all to changes pH biological range. Here, we report on sensing strategy conformational directly modifies quantum yield and lifetime circular permutated turquoise fluorescent protein. absolute parameter that...
Rho GTPases are regulatory proteins, which orchestrate cell features such as morphology, polarity and movement. Therefore, probing GTPase activity is key to understanding processes development migration. Localization-based reporters for active attractive probes study GTPase-mediated in real time with subcellular resolution living cells tissue. Until now, relocation biosensors (sensors that relocalize the native location of GTPase) seem have been only useful certain organisms not...
Vascular endothelial-cadherin (VE-cadherin) controls endothelial cell-cell adhesion and preserves integrity. In order to maintain barrier function, VE-cadherin function is tightly regulated through mechanisms that involve protein phosphorylation cytoskeletal dynamics. Here, we show loss of results in intercellular gap formation a drop electrical resistance monolayers primary human cells. Detailed analysis revealed adhesion, induced by VE-cadherin-blocking antibodies, preceded dependent on...
To elucidate the downstream mechanisms of vascular endothelial growth factor receptor 2 (VEGFR2), a key in angiogenesis, which has been associated with atherosclerotic plaque and instability.By using yeast-2-hybrid assay, we identified A Disintegrin And Metalloprotease 10 (ADAM10) as novel binding partner VEGFR2. ADAM10 is metalloprotease sheddase activity involved cell migration; however, its exact function cells (ECs), atherosclerosis largely unknown. For first time to our knowledge, show...
Impaired endothelial barrier function results in a persistent increase permeability and vascular leakage. Repair of dysfunctional requires controlled restoration adherens junctions, comprising (VE)-cadherin associated β-, γ-, α-, p120-catenins. Little is known about the mechanisms by which recovery VE-cadherin–mediated cell–cell junctions regulated. Using inflammatory mediator thrombin, we demonstrate an important role for Src homology 2-domain containing tyrosine phosphatase (SHP2)...
Leukocyte transendothelial migration involves the active participation of endothelium through formation apical membrane protrusions that embrace adherent leukocytes, termed docking structures. Using live-cell imaging, we find prior to transmigration, endothelial structures form around 80% all neutrophils. Previously showed RhoG and SGEF control leukocyte transmigration. In this study, our data reveal both full-length Trio first DH-PH (TrioD1) domain Trio, which can activate Rac1 RhoG,...