A5086632006- Lymphatic System and Diseases
- Angiogenesis and VEGF in Cancer
- Lymphatic Disorders and Treatments
- Cerebrospinal fluid and hydrocephalus
- Neurotransmitter Receptor Influence on Behavior
- Axon Guidance and Neuronal Signaling
- Vascular Malformations and Hemangiomas
- Spinal Dysraphism and Malformations
- Developmental Biology and Gene Regulation
- Cell Adhesion Molecules Research
- Sympathectomy and Hyperhidrosis Treatments
- Neuroscience and Neuropharmacology Research
- Cholesterol and Lipid Metabolism
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Liver physiology and pathology
- Thermoregulation and physiological responses
- Clinical Reasoning and Diagnostic Skills
- Hematopoietic Stem Cell Transplantation
- Cellular Mechanics and Interactions
- Biomarkers in Disease Mechanisms
- Intracerebral and Subarachnoid Hemorrhage Research
- Mesenchymal stem cell research
- Hippo pathway signaling and YAP/TAZ
- Cardiac Fibrosis and Remodeling
Wihuri Research Institute
2013-2024
University of Helsinki
2013-2024
Translational Research in Oncology
2020
Finnish Institute for Health and Welfare
2009-2015
Institute for Molecular Medicine Finland
2011-2014
University of Colorado Denver
2014
University of Colorado Anschutz Medical Campus
2014
University of Eastern Finland
2014
Kuopio University Hospital
2014
The skin interstitium sequesters excess Na+ and Cl- in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense hypertonic electrolyte accumulation activate tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) initiate expression secretion of VEGFC, which enhances clearance via cutaneous lymph vessels increases eNOS blood vessels. It is unclear whether this local MPS response osmotic stress important systemic pressure...
The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement neuropathological processes, yet little is known about development or maintenance. We show here that LVs develop postnatally, appearing first around the foramina basal parts skull and spinal canal, sprouting along blood cranial nerves to various meninges surrounding central nervous system (CNS). VEGF-C, expressed mainly vascular smooth muscle cells, VEGFR3 endothelial cells were...
Angiopoietins regulate vascular homeostasis via the endothelial Tie receptor tyrosine kinases. Angiopoietin-1 (Ang1) supports stabilization Tie2 activation. Angiopoietin-2 (Ang2) functions as a context-dependent agonist/antagonist promoting pathological angiogenesis, permeability and inflammation. Elucidating Ang2-dependent mechanisms of destablization is critical for rational design angiopoietin antagonists that have demonstrated therapeutic efficacy in cancer trials. Here, we report Ang2,...
In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with lymphatic vascular system, it unknown whether SC a blood or vessel. Here, we demonstrated expression of endothelial cell markers by in murine zebrafish models as well human eye tissue. The initial stages development involved induction transcription factor PROX1 lymphangiogenic receptor tyrosine kinase VEGFR-3 venous cells postnatal mice. Using gene deletion...
Report12 October 2015Open Access VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption Harri Nurmi Wihuri Research Institute Translational Cancer Biology Program, Biomedicum Helsinki, University of Finland Search more papers by this author Pipsa Saharinen Georgia Zarkada Wei Zheng Marius R Robciuc Kari Alitalo Corresponding Author Information Nurmi1, Saharinen1, Zarkada1, Zheng1, Robciuc1,‡ 1,‡ 1Wihuri ‡These authors contributed equally to work *Corresponding...
Abstract Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest their possible involvement Alzheimer’s disease (AD). Here we find APdE9 and 5xFAD mouse models AD, amyloid-β (Aβ) is confined to blood dLV morphology or function not altered. The induction sustained atrophy hyperplasia AD mice by blocking overexpressing C, impaired improved, respectively, macromolecular...
The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to blood circulation. We showed previously that Prox1 dosage development of vasculature. lack activity results in complete absence endothelial cells (LECs). In heterozygous embryos, number LECs reduced because a decrease progenitor pool cardinal vein. This reduction caused by some being unable maintain expression. this study, we identified Vegfr3 , cognate receptor lymphangiogenic...
The purpose of the present study was to investigate role ventral pallidal opioidergic mechanisms in control ethanol intake by studying effects acute administration morphine on levels GABA, glutamate, and dopamine pallidum. conducted using alcohol-preferring Alko Alcohol (AA) alcohol-avoiding Non-Alcohol (ANA) rat lines that have well-documented differences their voluntary brain systems. Therefore, examination neurobiological between is supposed help identify neuronal underlying intake, since...
Primitive lymphatic vessels are remodeled into functionally specialized initial and collecting lymphatics during development. Lymphatic endothelial cell (LEC) junctions in transform from a zipper-like to button-like pattern vessel development, but what regulates this process is largely unknown. Angiopoietin 2 (Ang2) deficiency leads abnormal vessels. Here we found that an ANG2-blocking antibody inhibited embryonic lymphangiogenesis, whereas endothelium-specific ANG2 overexpression induced...
Lymphangiogenesis is supported by 2 homologous VEGFR3 ligands, VEGFC and VEGFD. required for lymphatic development, while VEGFD not. are proteolytically cleaved after cell secretion in vitro, recent studies have implicated the protease a disintegrin metalloproteinase with thrombospondin motifs 3 (ADAMTS3) secreted factor collagen calcium binding EGF domains 1 (CCBE1) this process. It not well understood how ligand proteolysis controlled at molecular level or process regulates...
Abstract Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures embedded within vertebral tissues difficult to visualize using traditional histology. Here we show an extended column LV network three-dimensional imaging decalcified iDISCO + -clarified spine segments. Vertebral connect peripheral sensory sympathetic ganglia form...
Objective— Lymphatic vessels collect extravasated fluid and proteins from tissues to blood circulation as well play an essential role in lipid metabolism by taking up intestinal chylomicrons. Previous studies have shown that impairment of lymphatic vessel function causes lymphedema fat accumulation, but clear connections between arterial pathologies not been described. Approach Results— Two transgenic mouse strains with insufficiency (soluble vascular endothelial growth factor 3 [sVEGFR3]...
Elevated serum levels of the lymphangiogenic factors VEGF-C and -D have been observed in obese individuals but their relevance for metabolic syndrome has remained unknown.
Neural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that hippocampal express vascular endothelial growth factor receptor (VEGFR) 3 and its ligand VEGF-C, which activates enter cell cycle generate Hippocampal neurogenesis impaired by conditional deletion Vegfr3 in...
The recent discovery of lymphatic vessels (LVs) in the dura mater, outermost layer meninges around central nervous system (CNS), has opened a possibility for development alternative therapeutics CNS disorders. vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential and maintenance dural LVs. However, its significance mediating function autoimmunity unclear. We show that inhibition VEGF-C/VEGFR3 using monoclonal VEGFR3-blocking antibody, soluble...
Abstract During plaque progression, inflammatory cells progressively accumulate in the adventitia, paralleled by an increased presence of leaky vasa vasorum. We here show that next to vasorum, also adventitial lymphatic capillary bed is expanding during development humans and mouse models atherosclerosis. Furthermore, we investigated role lymphatics atherosclerosis progression. Dissection draining lymph node vessel atherosclerotic ApoE −/− mice aggravated formation, which was accompanied...
Angiopoietin-2 (Ang2), a ligand of the endothelial Tie2 tyrosine kinase, is involved in vascular inflammation and leakage critically ill patients. However, role Ang2 demyelinating central nervous system (CNS) autoimmune diseases unknown. Here, we report that pathogenesis experimental encephalomyelitis (EAE), rodent model multiple sclerosis. expression was induced CNS autoimmunity, transgenic mice overexpressing specifically cells (ECs) developed significantly more severe EAE. In contrast,...
Background and Aims Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable humans because of major species differences. Liver‐humanized (LHM) considered a promising model hepatic systemic metabolism. Therefore, we aimed further explore their lipoprotein metabolism characterize key species‐related, physiological Approach Results Fah−/− , Rag2−/− Il2rg−/− knockout on nonobese diabetic (FRGN) background were repopulated...