Endothelial Cell News Volume 3.28 | Aug 20 2018

TOP STORY

A Linked Organ-on-Chip Model of the Human Neurovascular Unit Reveals the Metabolic Coupling of Endothelial and Neuronal Cells

Three coupled chips modeled influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. Scientists used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. [Nat Biotechnol] Abstract | Press Release

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SUMOylation of VEGFR2 Regulates Its Intracellular Trafficking and Pathological Angiogenesis

Researchers showed that endothelial-specific deletion of the SUMO endopeptidase SENP1 reduced pathological angiogenesis and tissue repair during hindlimb ischemia, and VEGF-induced angiogenesis in the cornea, retina, and ear. SENP1-deficient endothelial cells showed increased SUMOylation of VEGFR2 and impaired VEGFR2 signaling. [Nat Commun] Full Article

Targeting the Tie2–α_vβ₃ Integrin Axis with Bi-Specific Reagents for the Inhibition of Angiogenesis

The bi-specific antagonists targeting both Tie2 and α_vβ₃ integrin inhibited adhesion and proliferation of endothelial cells cultured together with the α_vβ₃ integrin ligand vitronectin, as well as endothelial cell invasion and tube formation. [BMC Biol] Full Article

Phenotypic miRNA Screen Identifies miRNA-26b to Promote the Growth and Survival of Endothelial Cells

Scientists revealed that miR-26b enhanced endothelial cell growth and survival through inhibiting PTEN expression. Local administration of miR-26b mimics promoted the growth of new microvessels in the Matrigel plug model. [Mol Ther Nucleic Acids] Abstract | Full Article

Neuropilin-1 Maintains Dimethylarginine Dimethylaminohydrolase 1 Expression in Endothelial Cells, and Contributes to Protection from Angiotensin II-Induced Hypertension

Short hairpin RNA-mediated knockdown of neuropilin-1 (NRP1) reduced the level and mRNA stability of dimethylarginine dimethylaminohydrolase 1 (DDAH1) but not DDAH2 in HUVECs, whereas overexpression of NRP1 increased the mRNA stability of DDAH1. The regulation of NRP1 on DDAH1 expression was mediated by a posttranscriptional mechanism involving miR-219-5p in HUVECs. [FASEB J] Abstract

Soluble Endoglin Regulates Expression of Angiogenesis-Related Proteins and Induction of Arteriovenous Malformations in a Mouse Model of Hereditary Hemorrhagic Telangiectasia

Investigators found that soluble endoglin (sEng) downregulated several pro-angiogenic and pro-migratory proteins involved in angiogenesis. This effect was more reduced in endothelial cells that lacked endogenous transmembrane endoglin, suggesting that the anti-angiogenic activity of sEng is dependent on the presence of endogenous transmembrane endoglin protein. [Dis Model Mech] Abstract | Full Article

Phospholipidome of Endothelial Cells Shows a Different Adaptation Response upon Oxidative, Glycative and Lipoxidative Stress

H₂O₂ induced a more acute adaptation of the phospholipid (PL) profile than glucose or 4-hydroxynonenal (HNE). Unsaturated PL molecular species were up-regulated after 24 hour incubation with H₂O₂, while an opposite trend was observed in glucose- and HNE-treated cells. [Sci Rep] Full Article

TGF-β1-Induced SMAD2/3/4 Activation Promotes RELM-β Transcription to Modulate the Endothelium-Mesenchymal Transition in Human Endothelial Cells

Researchers found that TGF-β1 stimulation significantly upregulated resistin-like molecule-β (RELM-β) expression; RELM-β knockdown could attenuate TGF-β1-induced cell proliferation and migration of endothelial cell lines and changes in protein levels of endothelial-to-mesenchymal transition markers. [Int J Biochem Cell Biol] Abstract

Apatinib Targets Both Tumor and Endothelial Cells in Hepatocellular Carcinoma

Apatinib inhibited phosphorylation of VEGFR-2 in HUVECs and blocked in vitro endothelial cell migration and tube formation. Apatinib significantly inhibited VEGF-triggered VEGFR-2 phosphorylation and activation of downstream signaling molecules such as Akt and ERK1/2 in hepatocellular carcinoma cells. [Cancer Med] Abstract | Full Article

Effect of Catechins and High-Temperature-Processed Green Tea Extract on Scavenging Reactive Oxygen Species and Preventing Aβ_1–42 Fibrils’ Formation in Brain Microvascular Endothelium

Compared to Aβ_1–42-only treatment, pretreatment of high-temperature-processed green tea extract (HTP_GTE) was revealed to effectively inhibit reactive oxygen species generation. HTP_GTE and catechins not only inhibited Aβ_1–42 fibril formation but also destabilized preformed Aβ_1–42 fibrils. [Nutr Neurosci] Abstract

Rutacecarpine Inhibits Angiogenesis by Targeting the VEGFR2 and VEGFR2-Mediated Akt/mTOR/p70s6k Signaling Pathway

Scientists confirmed that rutacecarpine exhibited modest inhibitory activity against HUVECs and remarkable inhibitive effect against the migration and adhesion of HUVECs, as well as significant anti-angiogenesis activities in the chorioallantoic membrane assay. [Molecules] Full Article

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Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and Bacterial-Host Interactions Facilitate the Bacterial Pathogen Invading the Brain

The authors elucidate the different mechanisms of blood brain barrier disruption that may occur due to invasion by different types of bacteria, as well as show the bacteria-host interactions that assist the bacterial pathogen in invading the brain. [Cell Mol Neurobiol] Abstract

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FDA Approves EYLEA^® (Aflibercept) Injection sBLA in Wet Age-Related Macular Degeneration

Regeneron Pharmaceuticals, Inc. announced that the U.S. FDA has approved a supplemental Biologics License Application (sBLA) for EYLEA^® injection in patients with wet age-related macular degeneration. [Regeneron Pharmaceuticals, Inc.] Press Release

Eisai and Merck Announce FDA Approval of LENVIMA^® (Lenvatinib) Capsules for First-Line Treatment of Unresectable Hepatocellular Carcinoma (HCC)

Eisai Co., Ltd. and Merck & Co., Inc., announced that the U.S. FDA approved the kinase inhibitor LENVIMA^® for the first-line treatment of patients with unresectable HCC. [Eisai Co., Ltd.] Press Release

Over $16M Funding for New Health and Medical Research

The Federal Minister for Health, the Hon Greg Hunt MP, announced two Centres of Research Excellence in Clinical Research based at the University of Sydney were awarded almost $5 million in funding from the National Health and Medical Research Council. [The University of Sydney] Press Release

Salk Institute Asks Judge to Narrow Scope of Gender-Discrimination Suit

Lawyers representing the Salk Institute for Biological Studies went to court, asking a judge to narrow the scope of a gender-discrimination lawsuit filed by molecular biologist Beverly Emerson. [Nature News] Editorial

Prominent Health Policy Researcher Plagiarized Colleagues’ Work, Dartmouth Investigation Finds

A Dartmouth College investigation has concluded that Dr. H. Gilbert Welch, one of the country’s most prominent health care policy scholars, committed research misconduct in connection with a paper published in a top medical journal. [STAT News] Editorial

Top Geneticist Loses £3.5-Million Grant in First Test of Landmark Bullying Policy

One of the world’s largest research-funding charities has revoked a £3.5-million (US$4.5-million) grant awarded to a top cancer geneticist, Nazneen Rahman, following allegations that she bullied scientists and other staff when she worked at the Institute of Cancer Research in London. [Nature News] Editorial

NEW Gordon Research Seminar (GRS): Vascular Cell Communication and Signaling: Implications in Health and Disease
January 19-20, 2019
Ventura, California, United States

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NEW Faculty Positions – Cardiovascular Research (Nationwide Children’s Hospital, Research Institute)

Postdoctoral Fellow – Lymph Node Vasculature (Uppsala University)

Postdoctoral Fellow – Pulmonary Arterial Hypertension (National Institutes of Health)

Assistant Professor – Stem Cell and Organoid Medicine (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellow – Tumor and Autoimmune Pathogenesis (Stanford University)

Scientist – Cardiovascular Research (University of Iowa Hospital and Clinics)

Senior Postdoctoral Research Position – Cardiovascular Research (University of Tennessee)

Research Scientist – Corneal Cells (The Veneto Eye Bank Foundation)

Postdoctoral Research Assistant – Cancer and Vascular Biology (University of Oxford)

Postdoctoral Position – Cardiovascular Development and Congenital Heart Disease (Thomas Jefferson University)

Postdoctoral Fellow – Cardiovascular Stem Cell Biology (University of Illinois at Chicago)

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