Endothelial Cell News Volume 2.39 | Nov 27 2017

TOP STORY

Secret Alter Ego of Well-Known Protein Fights Leaky Blood Vessels

Scientists set out to solve the mystery of how blood flow keeps the vessels intact and, to their surprise, discovered a completely new cell signaling pathway that is a promising target for drugs to treat a variety of debilitating conditions. [Press release from the Wyss Institute at Harvard University discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Mechanotransduction-Modulated Fibrotic Microniches Reveal the Contribution of Angiogenesis in Liver Fibrosis

Researchers developed fibrotic microniches that recapitulate the interaction of liver sinusoid endothelial cells and hepatic stellate cells. They investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. [Nat Mater] Abstract

Social Stress Induces Neurovascular Pathology Promoting Depression

Scientists investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier permeability and infiltration of peripheral immune signals. They found reduced expression of the endothelial cell tight junction protein claudin-5 and abnormal blood vessel morphology in nucleus accumbens of stress-susceptible but not resilient mice. [Nat Neurosci] Abstract

R-Ras-Akt Axis Induces Endothelial Lumenogenesis and Regulates the Patency of Regenerating Vasculature

The authors showed that Akt activation by a Ras homolog, R-Ras, stabilizes the microtubule cytoskeleton in endothelial cells leading to endothelial lumenogenesis. The activation of Akt by the potent angiogenic factor VEGF-A did not strongly stabilize microtubules or sufficiently promote lumen formation, hence demonstrating a distinct role for the R-Ras-Akt axis. [Nat Commun] Full Article | Press Release

Development and Plasticity of Meningeal Lymphatic Vessels

Investigators showed that meningeal lymphatic vessels develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system. [J Exp Med] Abstract

NRF2 Regulates Endothelial Glycolysis and Proliferation with miR-93 and Mediates the Effects of Oxidized Phospholipids on Endothelial Activation

The authors investigated the molecular mechanisms of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine function with a special emphasis on NRF2-regulated miRNAs in HUVECs utilizing miRNA profiling, global run-on sequencing, genome-wide NRF2 binding model, and RNA sequencing with miRNA overexpression and silencing. [Nucleic Acids Res] Full Article

Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation

Investigators used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis model for multiple sclerosis. [Cell Rep] Full Article | Press Release | Graphical Abstract

Hematopoietic Substrate-1-Associated Protein X-1 Regulates the Proliferation and Apoptosis of Endothelial Progenitor Cells through Akt Pathway Modulation

The effect and mechanism of hematopoietic substrate-1-associated protein X-1 (HAX-1) on endothelial precursor cells (EPCs) remains unknown. Researchers investigated the effect of HAX-1 on the proliferation and apoptosis of EPCs and explored its mechanism. According to their results, HAX-1 was overexpressed in EPCs. [Stem Cells] Abstract

Carbon Monoxide Prevents TNF-α-Induced eNOS Downregulation by Inhibiting NF-κB-Responsive miR-155-5p Biogenesis

Scientists found that the carbon monoxide-releasing compound CORM-2 prevented tumor necrosis factor (TNF)-α-mediated decreases in endothelial nitric oxide synthase (eNOS) expression and nitric oxide/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. [Exp Mol Med] Full Article

Human Umbilical Vein Endothelium-Derived Exosomes Play a Role in Foetoplacental Endothelial Dysfunction in Gestational Diabetes Mellitus

HUVECs from women with gestational diabetes mellitus showed increased L-arginine transport via the human cationic amino acid transporter 1. Moreover, expression of endothelial nitric oxide synthase and nitric oxide synthesis were increased. [Biochim Biophys Acta] Abstract

Preclinical Evaluation and Optimization of a Cell Therapy Using Human Cord Blood-Derived Endothelial Colony-Forming Cells for Ischemic Retinopathies

Using a well-defined subpopulation of human cord blood-derived endothelial progenitors known as endothelial colony-forming cells, investigators evaluated essential requirements for further development of this cell therapy targeting the ischemic retina, including dose response, delivery route, and toxicity. [Stem Cells Transl Med] Full Article

TIMAP, the Versatile Protein Phosphatase 1 Regulator in Endothelial Cells

Transforming growth factor-β inhibited membrane associated protein (TIMAP) is abundant in endothelial cells. A growing body of evidence attained through characterization of newly identified protein partners calls attention to its critical role in normal and pathological activities of the endothelium via regulation of protein phosphatase 1. [IUBMB Life] Abstract

Visit our reviews page to see a complete list of reviews in the endothelial cell research field.

Regeneron Provides Update on EYLEA^® (Aflibercept) Injection and Nesvacumab (Ang2 Antibody) Combination Program

Regeneron Pharmaceuticals, Inc. announced that results from two Phase II studies that added the angiopoietin2 (Ang2) antibody nesvacumab to EYLEA^® injection did not provide sufficient differentiation to warrant Phase III development. The RUBY study evaluated patients with diabetic macular edema and the ONYX study evaluated patients with wet age-related macular degeneration. [Regeneron Pharmaceuticals, Inc.] Press Release

EUSA Pharma and AVEO Oncology Announce the First Commercial Launch of FOTIVDA^® (Tivozanib)

EUSA Pharma and AVEO Oncology announced the first commercial launch of FOTIVDA^® with the initiation of product sales in Germany. In the European Union, Norway and Iceland, tivozanib is indicated for the first line treatment of adult patients with advanced renal cell carcinoma (aRCC) and for adult patients who are VEGF receptor and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for aRCC. [AVEO Oncology] Press Release

Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage

Eager to speed development of revolutionary treatments, the Food and Drug Administration recently announced that it would expedite approval of experimental gene therapies. But the regulatory process may not be the biggest obstacle. [The New York Times] Editorial

Nobel Laureates Demand Release of Iranian Scholar Facing Death Sentence

Some 75 Nobel prizewinners have called on the Iranian government to release Ahmadreza Djalali, a researcher in disaster medicine who was sentenced to death last month. The letter is the latest and most powerful protest against the ruling by the scientific community so far. [Nature News] Editorial

Still No Science Advisor at the White House

Ten months into his presidency, Donald Trump has yet to name a science advisor. It’s the longest amount of time a modern president has taken to nominate someone to the position since at least 1976, when Congress established the White House’s Office of Science and Technology Policy. [MIT Technology Review] Editorial

NEW SYStem – Symposium for the Next Generation of Stem Cell Researchers
February 22-24, 2018
Vienna, Austria

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NEW Research Technologist – Mesenchymal and Endothelial Cells (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Physiology (The University of Tennessee Health Science Center)

PhD & Postdoctoral Positions – Neurovascular Biology (Université Libre de Bruxelles)

Principal Scientist – Cardiovascular Research (Novo Nordisk)

Postdoctoral Positions – Molecular Neurobiology (San Raffaele Institute)

Postdoctoral Fellow or Research Assistant Professor – Lung and Vascular Biology (Northwestern University)

Postdoctoral Research Fellow – Lung and Vascular Biology (University of Illinois at Chicago)

PhD Studentship – Cardiovascular Research (Max Planck Institute for Heart and Lung Research)

Postdoctoral Position – Basic Neuroscience (McLean Hospital/Harvard Medical School)

Postdoctoral Position – Biology of Blood Platelets (INSERM)

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