Endothelial Cell News Volume 3.31 | Sep 17 2018

TOP STORY

Paired-Cell Sequencing Enables Spatial Gene Expression Mapping of Liver Endothelial Cells

Scientists used paired-cell sequencing, in which mRNA from pairs of attached mouse cells were sequenced and gene expression from one cell type was used to infer the pairs’ tissue coordinates. They applied this method to pairs of hepatocytes and liver endothelial cells. [Nat Biotechnol] Abstract

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Toll-Like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension

TLR3 expression was reduced in pulmonary arterial hypertension (PAH) patient lung tissue and endothelial cells, and TLR3^-/- mice exhibited more severe pulmonary hypertension following exposure to chronic hypoxia/SU5416. TLR3 knockdown promoted double-stranded RNA signaling via other intracellular RNA receptors in endothelial cells and this was associated with greater susceptibility to apoptosis. [Am J Respir Crit Care Med] Abstract | Editorial

Activation of Ras in the Vascular Endothelium Induces Brain Vascular Malformations and Hemorrhagic Stroke

The authors generated an endothelial-specific, inducible HRAS^V12 mouse model, which resulted in dilated, proliferative blood vessels in the brain, blood-brain barrier breakdown, intracerebral hemorrhage, and rapid lethality. Organoid morphogenesis models revealed abnormal cessation of proliferation, abnormalities in expression of tip and stalk genes, and a failure to properly form elongating tubes. [Cell Rep] Full Article | Graphical Abstract

Improving Angiogenic Potential of EPCs via Engineering with Synthetic Modified mRNAs

After the transfection of cells with synthetic mRNAs, significantly increased VEGF-A, SDF-1α, and ANG-1 protein levels were detected compared to untreated endothelial progenitor cells (EPCs). Thereby, mRNA engineered EPCs showed significantly increased chemotactic activity versus untreated EPCs and resulted in significantly improved attraction of EPCs. [Mol Ther Nucleic Acids] Full Article | Graphical Abstract

Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells through miR-195

Silence of lncRNA UCA1 repressed HMEC-1 cells viability, migration, tube formation, and induced apoptosis. Meanwhile, silence of lncRNA UCA1 significantly up-regulated miR-195 expression. [Cell Physiol Biochem] Full Article

Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells

Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary retinal vascular endothelial cells under high glucose conditions. In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose. While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to VEGF changes. [Cell Physiol Biochem] Full Article

The Regulation of miRNAs by Reconstituted High-Density Lipoproteins in Diabetes-Impaired Angiogenesis

Using a miRNA array, researchers found that reconstituted high-density lipoprotein inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. [Sci Rep] Full Article

A Multi-Cellular 3D Bioprinting Approach for Vascularized Heart Tissue Engineering Based on HUVECs and iPSC-Derived Cardiomyocytes

The authors obtained a 3D cardiac tissue compose of induced pluripotent cell-derived cardiomyocytes with a high orientation index imposed by the different defined geometries and blood vessel-like shapes generated by HUVECs which, as demonstrated by in vivo grafting, better support the integration of the engineered cardiac tissue with host’s vasculature. [Sci Rep] Full Article

Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation

In in vitro studies, activation of AMP-activated protein kinase did not alter the phosphorylation of eNOS on Ser1177, but increased its phosphorylation on Thr495. Depletion of AMPKα1 in cultured human endothelial cells decreased Thr495 phosphorylation without affecting Ser1177 phosphorylation. [Int J Mol Sci] Full Article

Repurposing Antimalarial Aminoquinolines and Related Compounds for Treatment of Retinal Neovascularization

Amodiaquine suppressed both apelin-and VEGF-induced endothelial tube formation. Intravitreal amodaiquine significantly reduced choroidal neovascularization (CNV) lesion volume in the laser-induced CNV mouse model, and showed no signs of ocular toxicity at the highest doses tested. [PLoS One] Full Article | Press Release

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Angiogenic lncRNAs: A Potential Therapeutic Target for Ischaemic Heart Disease

Scientists summarize the classification and functions of long noncoding RNAs (LncRNAs) and their roles in regulating angiogenesis and in ischaemic heart disease, in the context of an overview of therapeutic angiogenesis in clinical trials. [Life Sci] Abstract | Graphical Abstract

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Opthea Presents Phase I/IIa Data of OPT-302 in Wet AMD

Opthea Limited announced that new clinical data analysis from its completed Phase I/IIa trial of intravitreally injected OPT-302 with and without Lucentis^® for the treatment of wet AMD. [Press release from Opthea Limited (GlobeNewswire, Inc.) discussing research presented at the Retina Society 2018 Annual Meeting, San Francisco] Press Release

FDA to Review EYLEA (Aflibercept) Injection for the Treatment of Diabetic Retinopathy

Regeneron Pharmaceuticals, Inc. announced that the FDA has accepted for review the supplemental Biologics License Application of EYLEA^® injection for the treatment of diabetic retinopathy. [Regeneron Pharmaceuticals, Inc.] Press Release

Researcher Gets $2.4 Million Grant to Study Diabetic Vascular Diseases

Dr. Ming-Hui Zou, director of the Center for Molecular and Translational Medicine at Georgia State University, has received a four-year, $2.4 million federal grant to study cardiovascular complications in diabetes. [Georgia State University] Press Release

NIH Gets $2 Billion Boost in Final 2019 Spending Bill

Congress has approved a $2 billion raise, to $39.1 billion, for the National Institutes of Health (NIH) in a 2019 spending bill approved by House of Representatives and Senate negotiators. [ScienceInsider] Editorial

Patients vs. Paywalls: Is the U.S. Ready for Open-Access Publishing?

Scientific publishing giant Elsevier recently came under fire after its director of scholarly communications, William Gunn, wrote a controversial tweet in response to a post that “people shouldn’t have to jump through hoops” to access important medical research. [STAT News] Editorial

Evidence-Based Medicine Group in Turmoil after Expulsion of Co-Founder

A bitter dispute with one of its co-founders has plunged Cochrane, an international network of scientists promoting evidence-based medicine, into a crisis on the eve of an international gathering that marks its 25^th anniversary. A narrow majority of the organization’s Governing Board apparently decided to end the Cochrane membership of Peter Gøtzsche, director of the Nordic Cochrane Centre in Copenhagen and a member of the board himself, for causing “disrepute” to the organization. Four other board members then resigned in protest. [ScienceInsider] Editorial

NIH Set to Strengthen Its Sexual-Harassment Policies

The US National Institutes of Health (NIH) is remaking how it handles allegations of harassment by its employees. The agency will soon introduce a centralized system for reporting harassment by NIH scientists, director Francis Collins said. [Nature News] Editorial

NEW Joint Annual Scientific Meeting of the Australian Atherosclerosis Society, the Australian Vascular Biology Society and the High Blood Pressure Research Council of Australia 2018
November 27-30, 2018
Glenelg, Australia

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NEW Postdoctoral Scientists – Vascular Diseases (Oklahoma Medical Research Foundation)

Postdoctoral Scholar – Vascular Dysfunction in Sepsis (Medical University of South Carolina)

Postdoctoral Research Scientist – Microbiome Influence on Vascular Development & Function (Quadram Institute Bioscience)

Assistant Professor of Research – Organ-Associated Endothelial & Cardiomyocyte Regeneration (University of Maryland School of Medicine)

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)

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)

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