Endothelial Cell News Volume 1.35 | Dec 5 2016

TOP STORY

Structural Decoding of Netrin-4 Reveals a Regulatory Function Towards Mature Basement Membranes

The authors present the high-resolution structure of netrin-4, which showed unique features in comparison with netrin-1, and showed that it does not bind directly to any of the known netrin-1 receptors. They showed that netrin-4 disrupts laminin networks and basement membranes through high-affinity binding to the laminin γ1 chain. [Nat Commun] Full Article

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PI3 Kinase Inhibition Improves Vascular Malformations in Mouse Models of Hereditary Hemorrhagic Telangiectasia

Investigators showed that inducible, endothelial-specific homozygous activin receptor-like kinase 1 (Alk1) inactivation and bone morphogenetic proteins 9 and 10 ligand blockade both lead to arteriovenous malformations formation in postnatal retinal vessels and internal organs including the gastrointestinal tract in mice. [Nat Commun] Full Article | Press Release

Generating High-Purity Cardiac and Endothelial Derivatives from Patterned Mesoderm Using Human Pluripotent Stem Cells

Researchers provide a protocol that specifies cell fate efficiently into cardiac and endothelial lineages from human pluripotent stem cells (hPSCs). The protocol takes two weeks to complete and requires experience in hPSC culture and differentiation techniques. [Nat Protoc] Full Article

EphA2 Is a Functional Receptor for the Growth Factor Progranulin

Scientists discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. [J Cell Biol] Abstract | Press Release

Blood Vessel Endothelium-Directed Tumor Cell Streaming in Breast Tumors Requires the HGF/C-Met Signaling Pathway

Scientists investigated the importance of hepatocyte growth factor (HGF) signaling in the directional migration of breast tumor cells and how it might be integrated with the epidermal growth factor-colony-stimulating factor paracrine signaling loop to organize streaming towards blood vessels in vivo. [Oncogene] Full Article

PGC-1α Dictates Endothelial Function through Regulation of eNOS Expression

The authors sought to define the role of endothelial proliferator activated receptor gamma, coactivator 1α (PGC-1α) in vascular function using mice with endothelial specific loss of function and endothelial specific gain of function. [Sci Rep] Full Article

Glyoxalase 1-Knockdown in Human Aortic Endothelial Cells – Effect on the Proteome and Endothelial Function Estimates

Scientists investigated the effects of methylglyoxal (MG) accumulation by glyoxalase 1 (GLO1)-knockdown under hyperglycemic conditions in human aortic endothelial cells hypothesizing that the accumulation of MG accounts for the deleterious effects on vascular function. siRNA-mediated knockdown of GLO1 was performed and MG concentrations were determined. [Sci Rep] Full Article

Effects of Fatty Acid Synthase Inhibitors on Lymphatic Vessels: An In Vitro and In Vivo Study in a Melanoma Model

Researchers investigated the effects of pharmacological fatty acid synthase (FASN) inhibition on lymphatic vessels by using cell culture and mouse models. The effects of FASN inhibitors cerulenin and orlistat on the proliferation, apoptosis, and migration of human lymphatic endothelial cells were evaluated with in vitro models. The lymphatic outgrowth was evaluated by using a murine ex vivo assay. [Lab Invest] Abstract

Supportive Angiogenic and Osteogenic Differentiation of Mesenchymal Stromal Cells and Endothelial Cells in Monolayer and Co-Cultures

To determine how bone marrow-derived mesenchymal stromal cells (BMSCs) and endothelial cells (ECs) contribute to cellular proangiogenic differentiation, researchers analyzed the differentiation of BMSCs and ECs in standardized monolayer, Transwell and co-cultures. [Int J Oral Sci] Full Article

Suppression of NADPH Oxidase Attenuates Hypoxia-Induced Dysfunctions of Endothelial Progenitor Cells

Investigators evaluated the status of NADPH oxidases (NOX) in endothelial progenitor cells (EPCs) under hypoxic condition and to determine whether NOX inhibitors could attenuate hypoxia-induced dysfunctions of EPCs. [Biochem Biophys Res Commun] Abstract | Graphical Abstract

Endothelin-1 (ET-1) Stimulates Carboxy Terminal Smad2 Phosphorylation in Vascular Endothelial Cells by a Mechanism Dependent on ET Receptors and De Novo Protein Synthesis

The authors addressed the role and mechanisms involved in G protein-coupled receptor agonist, endothelin-1 (ET-1)-mediated transactivation of the transforming growth factor-β receptor in bovine aortic endothelial cells. [J Pharm Pharmacol] Abstract

Gene Delivery Nanoparticles to Modulate Angiogenesis

The authors summarize key factors targeted for therapeutic angiogenesis and anti-angiogenesis gene therapy, non-viral nanoparticle-mediated approaches to gene delivery, and recent gene therapy applications in pre-clinical and clinical trials for ischemia, tissue regeneration, cancer, and wet age-related macular degeneration. [Adv Drug Deliv Rev] Abstract | Graphical Abstract

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CTI BioPharma Presents Nonclinical Pharmacology Study Demonstrating Pacritinib Has Distinct Profile amongst JAK Inhibitors

CTI BioPharma Corp. announced the results of a translational pharmacology study comparing biomarker activity profiles for three JAK inhibitors: pacritinib, ruxolitinib and momelotinib, using the BioMAP^® Diversity PLUS panel of in vitro human primary cell-based systems. The results demonstrated distinct profiles amongst these JAK inhibitors and suggest that clinical responses are likely to be distinct with each agent. [Press release from CTI BioPharma Corp. discussing research presented at EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium, Munich] Press Release

Amgen and Allergan Submit Biosimilar Marketing Authorization Application to European Medicines Agency for ABP 215, a Biosimilar Candidate to Bevacizumab

Amgen and Allergan plc. announced the submission of a Marketing Authorization Application to the European Medicines Agency for ABP 215, a biosimilar candidate to Avastin^® (bevacizumab). ABP 215 is a biosimilar candidate to bevacizumab, a recombinant immunoglobulin G1 monoclonal antibody that binds to vascular endothelial growth factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors. [Amgen Inc.] Press Release

MedImmune and AbPro Enter into a Collaborative Agreement for a Novel Bispecific Antibody

MedImmune, the global biologics research and development arm of AstraZeneca, and Abpro, announced they have entered into a collaborative agreement to advance the development of a preclinical, novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor. [MedImmune] Press Release

Maryland Congressman in Running to Head NIH?

Representative Andy Harris, an anesthesiologist who has shown a keen interest in the National Institutes of Health (NIH) while in Congress, has put his hat in the ring for NIH director in the incoming administration of President-elect Donald Trump, he told ScienceInsider. Harris says he knows that some biomedical scientists would view him as a controversial choice, but argues that his blend of research and political experience would make him a good advocate for addressing NIH’s flaws and for growing the agency’s budget in a time of fiscal restraint. [ScienceInsider] Editorial

NEW Stem Cells and Regenerative Medicine 2^nd International Congress
April 19-21, 2017
Mashhad, Iran

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NEW Assistant Professor – Regenerative Medicine (University of Cincinnati)

Postdoctoral Position – Endothelial Interactions in Vascular Disease (University of Pittsburgh)

Postdoctoral Position – Intersectional Genetics (VIB)

Postdoctoral Associate – Neuroscience (University of Pittsburgh)

Postdoctoral Fellow – Vascular Cell Signaling (Louisiana State University Health Sciences Center)

Postdoctoral Fellowship – Vascular Biology and Genetics (Boston Children’s Hospital and Harvard Medical School)

Research Associate – Molecular Mechanisms underlying Abnormal Human Placental Vascular Function (University of Colorado Anschutz Medical Campus)

Senior Scientific Researcher – Molecular Oncology (Genentech)

Cell Biologist – Pulmonary Vascular Signaling and Endothelial Cell Biology (University of Maryland)

Postdoctoral Positions – Vascular and Immune Modulation in Cancer (VIB)

Research Specialist/Technician – Cardiovascular Diseases (University of Illinois Chicago College of Medicine)

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