A5003209132- Angiogenesis and VEGF in Cancer
- Lymphatic System and Diseases
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and disorders
- Vascular Malformations and Hemangiomas
- Cell Adhesion Molecules Research
- Lymphatic Disorders and Treatments
- Congenital heart defects research
- Virus-based gene therapy research
- Axon Guidance and Neuronal Signaling
- Spaceflight effects on biology
- Atherosclerosis and Cardiovascular Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Vascular Tumors and Angiosarcomas
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cardiac Fibrosis and Remodeling
- CRISPR and Genetic Engineering
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Receptor Mechanisms and Signaling
- Peroxisome Proliferator-Activated Receptors
- Mast cells and histamine
- Immune cells in cancer
- Viral Infections and Immunology Research
Wihuri Research Institute
2014-2024
University of Helsinki
2013-2023
Helsinki University Hospital
2010-2020
Spanish National Cancer Research Centre
2014
Hubrecht Institute for Developmental Biology and Stem Cell Research
2014
Uppsala University
2014
Eli Lilly (United States)
2014
Harvard University
2014
Boston Children's Hospital
2014
Institute for Molecular Medicine Finland
2009-2013
Aging is an established risk factor for vascular diseases, but aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that endothelial growth (VEGF) signaling insufficiency, which caused by increased production decoy receptors, drive physiological across multiple systems. Increasing VEGF prevented age-associated capillary loss, improved perfusion and function, extended life span. Healthier was evidenced favorable metabolism body composition...
Hennekam lymphangiectasia-lymphedema syndrome (Online Mendelian Inheritance in Man 235510) is a rare autosomal recessive disease, which associated with mutations the CCBE1 gene. Because of striking phenotypic similarity embryos lacking either Ccbe1 gene or lymphangiogenic growth factor Vegfc gene, we searched for collagen- and calcium-binding epidermal domains 1 (CCBE1) interactions vascular endothelial factor-C (VEGF-C) signaling pathway, critical embryonic adult lymphangiogenesis.By...
The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, vessel leakage. ANG1 is a Tie2 agonist that promotes stabilization in inflammation sepsis, whereas ANG2 context-dependent or antagonist. A limited understanding of ANG signaling mechanisms the orphan Tie1 has hindered development ANG/Tie-targeted therapeutics. Here, we determined both binding to increases Tie1-Tie2 interactions β1 integrin-dependent manner regulates...
Angiopoietin-2 (Ang2), a ligand for endothelial TEK (Tie2) tyrosine kinase receptor, is induced in hypoxic cells of tumors, where it promotes tumor angiogenesis and growth. However, the effects Ang2 on lymphangiogenesis metastasis are poorly characterized. We addressed effect progression using systemic overexpression mice carrying xenografts, endothelium-specific VEC-tTA/Tet-OS-Ang2 transgenic implanted with isogenic administration Ang2-blocking antibodies to tumor-bearing immunodeficient...
Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel formation through activation of three receptor tyrosine kinases, VEGFR-1, -2, -3. The extracellular domain VEGF receptors consists seven immunoglobulin homology domains, which, upon ligand binding, promote dimerization. Dimerization initiates transmembrane signaling, which activates the intracellular kinase receptor. VEGF-C stimulates lymphangiogenesis contributes to pathological angiogenesis via VEGFR-3. However,...
Background— Vascular endothelial growth factor-B (VEGF-B) binds to VEGF receptor-1 and neuropilin-1 is abundantly expressed in the heart, skeletal muscle, brown fat. The biological function of VEGF-B incompletely understood. Methods Results— Unlike placenta factor, which same receptors, adeno-associated viral delivery mouse or heart muscle induced very little angiogenesis, vascular permeability, inflammation. As previously reported for 167 isoform, transgenic mice rats expressing both...
Accumulating clinical observations implicate vascular inflammation as an underlying cause of coagulopathy in severely ill COVID-19 patients and it was recently suggested that SARS-CoV-2 virus particles infect endothelial cells. Here, we show cells do not express angiotensin-converting enzyme-2 (ACE2), the receptor. Instead, pericytes microvascular smooth muscle ACE2 organotypic manner. Pericyte deficiency leads to increased expression release Von Willebrand factor intravascular platelet...
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...
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key drivers of blood lymph vessel formation in development, but also several pathological processes. VEGF-C signaling through VEGFR-3 promotes lymphangiogenesis, which is a clinically relevant target for treating lymphatic insufficiency blocking tumor angiogenesis metastasis. The extracellular domain VEGFRs consists seven Ig homology domains; domains 1-3 (D1-3) responsible ligand binding, the membrane-proximal 4-7...
Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important learn where the receptor ACE2 expressed. Here we mapped expression during postnatal development in adulthood. Pericytes CNS, heart, pancreas express strongly, as do perineurial adrenal fibroblasts, whereas endothelial cells not at any location analyzed. In a number of other organs, pericytes ACE2, including lung instead expressed bronchial epithelium alveolar...
Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, mutations of ANGPT2 were recently found However, mechanistic basis Ang2 activity not fully understood. Here, we used deletion, blocking Abs, transgene induction, transfer to study how Ang2, its Tie2 receptor, Tie1 vessels. We...
The therapeutic potential of vascular endothelial growth factor (VEGF)-C and VEGF-D in skeletal muscle has been considerable interest as these factors have both angiogenic lymphangiogenic activities. Previous studies mainly used adenoviral gene delivery for short-term expression VEGF-C pig, rabbit, mouse muscles. Here we the activated mature forms expressed via recombinant adeno-associated virus (rAAV), which provides stable, long-lasting transgene various tissues including muscle. Mouse...
The endothelial Tie1 receptor is ligand-less, but interacts with the Tie2 for angiopoietins (Angpt). Angpt2 expressed in tumor blood vessels, and its blockade inhibits angiogenesis. Here we found that deletion from endothelium of adult mice angiogenesis growth by decreasing cell survival without affecting normal vasculature. Treatment VEGF or VEGFR-2 blocking antibodies similarly reduced growth; however, no additive inhibition was obtained targeting both VEGF/VEGFR-2. In contrast, treatment...
Mechanisms of the transition from compensatory hypertrophy to heart failure are poorly understood and roles vascular endothelial growth factors (VEGFs) in this process have not been fully clarified. We determined expression profile VEGFs relevant receptors during progression left ventricular (LVH). C57BL mice were exposed transversal aortic constriction (TAC) outcome was studied at different time points (1 day, 2, 4, 10 weeks). A clear phase (2 weeks after TAC) seen with following (4 TAC)....
Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression lymphangiogenic growth factor (vascular endothelial factor-C [VEGF-C]) promote lymphatic and maturation tract. Unexpectedly, perinatal VEGF-C epithelium led resembling...
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...