Endothelial Cell News Volume 4.19 | Jun 3 2019

TOP STORY

Single Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations

Clustering analysis of gene expression from aortic cells identified ten populations of cells representing each of the main arterial cell types-fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the three distinct EC populations. [Circulation] Abstract

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Modeling Cardiovascular Risks of E-Cigarettes with Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells

Human-induced pluripotent stem cell-derived endothelial cells and a high-throughput screening approach were used to assess endothelial integrity following exposure to six different e-liquids with varying nicotine concentrations and to serum from e-cigarette users. [J Am Coll Cardiol] Abstract | Press Release | Graphical Abstract

Endophilin-A2 Dependent VEGFR2 Endocytosis Promotes Sprouting Angiogenesis

Scientists identified endophilin-A2 (ENDOA2), a BAR-domain protein that orchestrates CLATHRIN-independent internalization, as a critical mediator of endothelial cell migration and sprouting angiogenesis. They showed that EndoA2 knockout mice exhibited postnatal angiogenesis defects and impaired front-rear polarization of sprouting tip cells. [Nat Commun] Full Article

Lysolipid Receptor Cross-Talk Regulates Lymphatic Endothelial Junctions in Lymph Nodes

Using a genome-wide CRISPR/dCas9-based G protein-coupled receptor signaling screen, lysophosphatidic acid receptor 1 (LPAR1) was identified as an inducer of sphingosine 1-phosphate R1 (S1PR1)/β-arrestin coupling while suppressing Gαi signaling. S1pr1 and Lpar1-positive lymphatic endothelial cells of lymph nodes exhibited constitutive S1PR1/β-arrestin signaling, which was suppressed by LPAR1 antagonism. [J Exp Med] Abstract | Graphical Abstract

Single-Cell Transcriptional Profiling of Aortic Endothelium Identifies a Hierarchy from Endovascular Progenitors to Differentiated Cells

Using mitochondrial activity assays and phenotyping, investigators confirmed that endovascular progenitors displayed higher mitochondrial content compared to differentiated endothelial cells. The identities of these populations were further validated against bulk RNA sequencing data obtained from normal and tumor-derived vasculature. [Cell Rep] Full Article | Press Release | Graphical Abstract

Thermal Inkjet Bioprinting Triggers the Activation of the VEGF Pathway in Human Microvascular Endothelial Cells In Vitro

The authors previously showed that thermal inkjet bioprinted human microvascular endothelial cells were recruited or otherwise involved in the formation of microvasculature to form graft-host anastomoses upon implantation. In the present study they quantified and characterized the expression and activation of specific cytokines and kinases in vitro. [Biofabrication] Abstract

Agonist at PPARδ Mitigates Endothelial Dysfunction via Induction of Dihydrofolate Reductase Gene and Activation of BH₄ Salvage Pathway

Researchers examined the role of peroxisome proliferator-activated receptor δ (PPARδ) in the regulation of dihydrofolate reductase (DHFR), a key enzyme in the tetrahydrobiopterin (BH₄) salvage pathway. PPARδ agonist GW501516 increased DHFR and BH₄ in endothelial cells. The effect was blocked by PPARδ antagonist GSK0660. [Br J Pharmacol] Abstract

Binding Heterogeneity of Plasmodium falciparum to Engineered 3D Brain Microvessels Is Mediated by EPCR and ICAM-1

Scientists generated an engineered 3D human brain endothelial microvessel model and studied P. falciparum binding under the large range of physiological flow velocities that occur in both health and disease. Perfusion assays on 3D microvessels revealed previously unappreciated phenotypic heterogeneity in parasite binding to tumor necrosis factor alpha-activated brain endothelial cells. [MBio] Full Article

EGFL7 Mediates BMP9-Induced Sprouting Angiogenesis of Endothelial Cells Derived from Human Embryonic Stem Cells

Researchers showed that the secreted angiogenic factor epidermal growth factor-like domain 7 (EGFL7) was a downstream target of bone morphogenetic protein 9 (BMP9)-SMAD1/5-mediated signaling, and that EGFL7 promoted expansion of the endothelium via interference with NOTCH signaling, activation of ERK, and remodeling of the extracellular matrix. [Stem Cell Reports] Full Article | Graphical Abstract

Glycocalyx Regulation of Vascular Endothelial Growth Factor Receptor 2 Activity

Investigators showed that although VEGF stimulation promoted VEGFR2 internalization in control endothelial cells (ECs), loss of endomucin (EMCN) prevented VEGFR2 endocytosis. Cell surface analysis revealed a decrease in VEGFR2 following VEGF stimulation in control but not siRNA directed against EMCN-transfected ECs. EMCN depletion resulted in heightened phosphorylation following VEGF stimulation with an increase in total VEGFR2 protein. [FASEB J] Abstract

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CXC Chemokine Ligand 12 (CXCL12) in Atherosclerosis: An Underlying Therapeutic Target

The authors focus on recent advances in CXCL12 research in the pathogenesis of atherosclerosis together with its clinical values. This may provide insight into potential novel therapies for atherosclerosis. [Clin Chim Acta] Abstract

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Outlook Therapeutics Signs Manufacturing Supply Agreement with FUJIFILM Diosynth Biotechnologies as Part of Commercialization Strategy for ONS-5010

Outlook Therapeutics, Inc. announced that it has signed a master services agreement with FUJIFILM Diosynth Biotechnologies for the production of ONS-5010. ONS-5010 is a proprietary ophthalmic formulation of bevacizumab to be administered as an intravitreal injection for the treatment of wet AMD and other retina diseases. [Outlook Therapeutics, Inc.] Press Release

REGENXBIO Announces Completion of Dosing for Phase I/IIa Clinical Trial of RGX-314 in Wet AMD

REGENXBIO, Inc. announced it completed dosing across all five cohorts in the Phase I/IIa clinical trial of RGX-314 for the treatment of wet age-related macular degeneration (AMD). The study includes subjects previously treated for wet AMD who are responsive to anti-VEGF therapy. [REGENXBIO, Inc.] Press Release

Karolinska Institutet, KTH and Stockholm University Form the University Alliance Stockholm Trio

An international type model of a university alliance will be established between Karolinska Institutet, KTH and Stockholm University. The aim is to strengthen the development of the Stockholm region and to highlight the internationally distinguished research and education environment that the three universities constitute together. [Stockholm University] Press Release

US Science Academy Approves Plan to Oust Sexual Harassers

The US National Academy of Sciences has approved an amendment to its by-laws that allows its governing council to expel members for misconduct, including proven cases of sexual harassment. [Nature News] Editorial

Chinese American Scientists Uneasy Amid Crackdown on Foreign Influence

Government-instigated investigations that have led US research institutions to seek the dismissal of at least five ethnically Chinese scientists are fueling fears that researchers of Chinese descent are being unfairly targeted, although the government agency involved denies this, as does one of the research institutions. [Nature News] Editorial

NEW 3^rd International Conference on Stem Cells
October 3, 2019
Chania, Greece

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NEW Postdoctoral Fellowship – Neurovascular Imaging Research (University of Nevada)

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

Professorship Position – Vascular Metabolism (Johann Wolfgang Goethe-Universität Frankfurt)

Postdoctoral Researcher – Thrombotic & Inflammatory Diseases (Baker Heart and Diabetes Institute)

Postdoctoral Fellow – Cardiovascular Diseases (Rutgers University)

Faculty Position – Vision Science (The University of Tennessee Health Science Center)

Postdoctoral Research Associate – Blood-Brain Barrier & Neurovascular Research (Vanderbilt University)

Postdoctoral Position – The Vascular System in the Brain (Uppsala University)

Postdoctoral Position – Angiogenesis & Vascular Biology (Johns Hopkins University)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis)

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