A5067572575- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Cell Adhesion Molecules Research
- Acute Ischemic Stroke Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Congenital heart defects research
- Platelet Disorders and Treatments
- Intracerebral and Subarachnoid Hemorrhage Research
- Neonatal Respiratory Health Research
- Chronic Myeloid Leukemia Treatments
- Barrier Structure and Function Studies
- Lipid metabolism and disorders
- Lymphatic System and Diseases
- Blood Coagulation and Thrombosis Mechanisms
- Nerve Injury and Rehabilitation
- Phagocytosis and Immune Regulation
- Spinal Cord Injury Research
- Multiple Sclerosis Research Studies
- Spinal Hematomas and Complications
- Congenital Diaphragmatic Hernia Studies
- Analytical Chemistry and Chromatography
- Axial and Atropisomeric Chirality Synthesis
- Zebrafish Biomedical Research Applications
- Chemical Synthesis and Analysis
- Synthesis and Reactions of Organic Compounds
Karolinska Institutet
2015-2025
Bristol-Myers Squibb (Germany)
2023
Novartis (Germany)
2023
Karolinska University Hospital
2015
AstraZeneca (Brazil)
2015
Laerdal (Norway)
2015
Stockholm County Council
1985-2012
Uppsala University
1985-2010
Ludwig Cancer Research
2006
Medical University of Vienna
2006
Melagatran, a new, competitive and rapid inhibitor of thrombin with molecular mass 429 Da is described. Melagatran well tolerated when administered in very high doses, the oral bioavailability dog relatively high. The aim study was to determine, preclinical setting, degree selectivity against fibrinolytic system required for entering clinical development phase. compared two structurally similar inhibitors, inogatran H 317/86. potent inhibition by melagatran demonstrated low constant (Ki)...
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, therapy is associated an increased risk intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during tPA acting on parenchymal side neurovascular unit (NVU) increase blood–brain barrier (BBB) permeability and ICH through activation latent platelet-derived growth factor-CC (PDGF-CC) signaling by PDGF receptor-α (PDGFRα). However, in...
Ischemic stroke is a major cause of adult disability. Early treatment with thrombolytics and/or thrombectomy can significantly improve outcomes; however, following these acute interventions, limited to rehabilitation therapies. Thus, the identification therapeutic strategies that help restore brain function in post-acute phase remains challenge. Here we report genetic or pharmacologic inhibition PDGF-CC/PDGFRα pathway, which has previously been implicated pathology, reduced myofibroblast...
Pericytes are members of the tumor stroma; however, little is known about their origin, function, or interaction with other components. Emerging evidence suggest that pericytes may regulate leukocyte transmigration. Myeloid-derived suppressor cells (MDSC) immature myeloid powerful inhibitory effects on T-cell-mediated antitumor reactivity.We generated subcutaneous tumors in a genetic mouse model pericyte deficiency (the pdgfb (ret/ret) mouse) and littermate control mice (n = 6-25). Gene...
Disruption of blood-brain barrier (BBB) integrity is a feature various neurological disorders. Here we found that the BBB differently affected during preclinical, progression and remission phase experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis (MS). We have identified upregulation pro-inflammatory pro-angiogenic factors in transcriptome down-regulation endothelial tight junction members coinciding with elevated leakage specifically phase. These changes were...
Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of vasorelaxant acetylcholine (ACh), regulate integral to cholinergic antiinflammatory pathway in an inflammatory reflex mice. Here, we found that human cell ChAT mRNA expression was induced by activation involving PI3K signaling cascade. Mechanistically, identified following attenuation RE-1 Silencing...
Central nervous system (CNS) disorders such as ischemic stroke, multiple sclerosis (MS) or Alzheimeŕs disease are characterized by the loss of blood-brain barrier (BBB) integrity. Here we demonstrate that small tyrosine kinase inhibitor imatinib enhances BBB integrity in experimental autoimmune encephalomyelitis, an animal model (MS). Treatment was accompanied decreased CNS inflammation and demyelination especially reduced T-cell recruitment. This supported downregulation chemokine receptor...
We investigated whether imatinib (Gleevec®, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion injury were treated orally with for 5 days beginning 30 minutes after found that significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder as well attenuated astrogliosis deposition of chondroitin sulfate proteoglycans, increased tissue...
Platelet-derived growth factors (PDGFs) and their tyrosine kinase receptors (PDGFRs) are known to play important roles during development of the lungs, central nervous system (CNS), skeleton in several diseases. PDGF-C is a ligand for receptor PDGFRα. Mutations gene encoding have been linked clefts lip and/or palate humans, ablation 129/Sv background mice results death perinatal period. In this study, we report that C57BL/6 milder phenotype than mice, present phenotypic characterization...
Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and preventing further damage from the secondary consequences of TBI. A major complication TBI is cerebral edema, which can be caused by loss blood barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation latent platelet derived growth factor-CC (PDGF-CC) within promote BBB permeability through PDGF receptor α (PDGFRα) signaling, blocking this pathway improves outcomes. In...
The purpose of this study was to establish a model system for lymph vessel development based on directed differentiation murine embryonic stem cells.Stem cells were aggregated form embryoid bodies, and subsequently cultured in 3-dimensional collagen matrix up 18 days. Treatment with vascular endothelial growth factor (VEGF)-C VEGF-A individually enhanced formation lymphatic structures, although combined treatment VEGF-C most potent gave rise network LYVE-1, podoplanin, Prox1, VEGF receptor-3...
ABSTRACT Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFRα. Analysis Pdgfc null mice has demonstrated roles PDGF-C in palate closure and formation cerebral ventricles, but redundancy with other PDGFRα might obscure additional functions. In search further developmental PDGF-C, we generated that were double mutants Pdgfc−/− PdgfraGFP/+. These display a range severe phenotypes including spina bifida, lung emphysema, abnormal meninges...
Article24 May 2020Open Access Source Data VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content Christine Moessinger Vascular Biology Division, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden Search for more papers this author Ingrid Nilsson Lars Muhl Manuel Zeitelhofer Benjamin Heller Sahlgren Josefin Skogsberg Ulf Eriksson Corresponding Author [email protected] orcid.org/0000-0002-4439-3980...
The current standard of care for moderate to severe ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA). Treatment tPA can significantly improve neurological outcomes; however, associated an increased risk intracerebral hemorrhage (ICH). limits the use and identifying pathways induced by that increase this could provide new therapeutic options extend a wider patient population. Here, we investigate role protein kinase (PK)Cβ phosphorylation tight junction occludin...
Reduced tissue oxygen tension (hypoxia) is appreciated as an efficient stimulus for neovascularization. The effect of hypoxia on the very first stages vascular development is, however, less well characterized. Here we show that hypoxic conditions (1% O2) potently stimulated formation extensive network during a discrete stage mouse embryonal stem cell differentiation. morphological changes correlated with expanding pool endothelial cells and activation growth factor-d (Vegf-d) Vegf receptor-3...
A novel series of neutral thrombin inhibitors has been developed using a selection process based on docking experiments and property calculations predictions.
Abstract Type 2 diabetes mellitus (T2DM) affects millions of people and is linked with obesity lipid accumulation in peripheral tissues. Increased handling lipotoxicity insulin producing β-cells may contribute to β-cell dysfunction T2DM. The vascular endothelial growth factor (VEGF)-B regulates uptake transcytosis long-chain fatty acids over the endothelium tissues such as heart skeletal muscle. Systemic inhibition VEGF-B signaling prevents tissue accumulation, improves sensitivity glucose...
Selection of the best medical students among applicants is debated and many different methods are used. Academic merits predict good academic performance, but admitted by other pathways need not be less successful. The aim this study, was to compare communication skills between school through interviews or on merits, respectively. A retrospective cohort study. Communication at a surgical OSCE in 2008 were assessed independently two observers using an evaluative rating scale. Correlations,...