Endothelial Cell News Volume 4.20 | Jun 10 2019

TOP STORY

Single-Cell Transcriptome Analyses Reveal Novel Targets Modulating Cardiac Neovascularization by Resident Endothelial Cells Following Myocardial Infarction

An endothelial cell (EC)-specific multispectral lineage-tracing mouse was used to demonstrate that structural integrity of adult cardiac endothelium following myocardial infarction was maintained through clonal proliferation by resident ECs in the infarct border region, without significant contributions from bone marrow cells or endothelial-to-mesenchymal transition. [Eur Heart J] Full Article

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Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications

Using Organ-Chip technology, scientists created an entirely human blood-brain barrier-chip with induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial-like cells (iBMECs), astrocytes, and neurons. The iBMECs formed a tight monolayer that expressed markers specific to brain vasculature. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Cholinergic Neural Activity Directs Retinal Layer-Specific Angiogenesis and Blood Retinal Barrier Formation

Investigators report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevented invasion of endothelial cells into the deep layers of the retina and caused blood-retinal-barrier (BRB) dysfunction in mice. VEGF and Norrin, a Wnt ligand that induces BRB properties, were decreased after activity blockade. [Nat Commun] Full Article

AKAP12 Deficiency Impairs VEGF-Induced Endothelial Cell Migration and Sprouting

The consequences of siRNA-mediated downregulation A anchoring protein 12 (AKAP12) were studied in primary cultures of human endothelial cells as well as in endothelial cells and retinas from wild-type versus AKAP12^-/- mice. Molecular interactions were investigated using a combination of immunoprecipitation and mass spectrometry. [Acta Physiol (Oxf)] Abstract

ssODN-Mediated In-Frame Deletion with CRISPR/Cas9 to Restore the FVIII Function in Hemophilia A Patient-Derived iPSCs and ECs

The authors describe an efficient gene correction via single-stranded oligodeoxynucleotide (ssODN)-mediated in-frame deletion within the B domain of F8 with CRISPR/Cas9 in hemophilia A (HA) patient-derived induced pluripotent stem cells (HA-iPSCs). The expression and activity of FVIII was restored in corrected HA-iPSC-derived endothelial progenitor cells in vitro and in vivo. [Mol Ther Nucleic Acids] Abstract | Full Article | Graphical Abstract

SALM4 Regulates Angiogenic Functions in Endothelial Cells through VEGFR2 Phosphorylation at Tyr1175

Synaptic adhesion-like molecule 4 (SALM4) silencing in HUVECs and Salm4 knockout in lung endothelial cells (ECs) of Salm4^−/− mice suppressed phosphorylation of VEGFR2 tyrosine (Y) 1175 and downstream signaling upon VEGF-A stimulation. However, VEGFR2 phosphorylation at Y951 and Y1214 remained unchanged. [FASEB J] Abstract

Phosphodiesterase 3B (PDE3B) Antagonizes the Anti-Angiogenic Actions of PKA in Human and Murine Endothelial Cells

Investigators examined whether phosphodiesterases (PDEs) coordinated the actions of protein kinase A (PKA) during endothelial cell sprouting. Inhibiting each of the cAMP-hydrolyzing PDEs expressed in human endothelial cells revealed that PDE3 inhibition with cilostamide reduced angiogenic sprouting in vitro, while inhibitors of PDE2 and PDE4 family enzymes had no such effect. [Cell Signal] Abstract

The Human Glomerular Endothelial Cells Are Potent Pro-Inflammatory Contributors in an In Vitro Model of Lupus Nephritis

As the exact role of human renal glomerular endothelial cells (GEnCs) in lupus nephritis (LN) has not been fully elucidated, researchers investigated their involvement in LN. Conditionally immortalized human GEnCs were treated with pro-inflammatory cytokines known to be involved in LN pathogenesis and also with LPS. Secretion and surface expression of pro-inflammatory proteins were quantified via ELISA and flow cytometry. [Sci Rep] Full Article

ELK3 Expressed in Lymphatic Endothelial Cells Promotes Breast Cancer Progression and Metastasis through Exosomal miRNAs

Suppression of ELK3 in lymphatic endothelial cells (LECs) diminished the ability of LECs to promote tumor growth and metastasis of MDA-MB-231 in vivo. Exosomes derived from LECs significantly increased the migration and invasion of MDA-MB-231 in vitro, but ELK3 suppression significantly diminished the pro-oncogenic activity of exosomes from LECs. [Sci Rep] Full Article

The Role of Vitamin D in Cell-Cell Interaction of Fetal Endothelial Progenitor Cells and Umbilical Cord Endothelial Cells in a Preeclampsia-Like Model

Preeclampsia (PE) cord serum reduced the invasion of fetal endothelial colony-forming cells (ECFCs) into HUVEC monolayers or tubule networks. Vitamin D attenuated these effects of PE fetal serum on endothelial functional properties. Immunocytochemical studies revealed involvement of VE-cadherin contacts in interactions between ECFCs and mature fetal endothelial cells. [Am J Physiol Cell Physiol] Abstract

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Building Blood Vessels—One Rho GTPase at a Time

The authors provide an overview of Rho GTPase signaling contributions to endothelial cell (EC) vasculogenesis, angiogenesis, and mature vessel barrier function. A particular emphasis is placed on so-called “alternative” Rho GTPases, as they are largely understudied despite their likely important contributions to EC biology. [Cells] Full Article

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

CStone and Bayer Announce Global Collaboration to Evaluate PD-L1 Monoclonal Antibody CS1001 in Combination with Regorafenib

CStone Pharmaceuticals announced that the company has entered into a global clinical collaboration with China focus with Bayer HealthCare LLC to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of its PD-L1 monoclonal antibody CS1001 in combination with Bayer’s regorafenib, an oral multi-kinase inhibitor, as a treatment for multiple cancers including gastric cancer. [CStone Pharmaceuticals] Press Release

Aerpio Initiates Phase Ib Clinical Trial of Topical Ocular Formulation of AKB-9778 for Primary Open Angle Glaucoma

Aerpio Pharmaceuticals, Inc. announced dosing of the first subject in a Phase Ib trial of a topical ocular formulation of AKB-9778 in development for treatment of primary open angle glaucoma. AKB-9778 binds to and inhibits vascular endothelial protein tyrosine phosphatase, an important negative regulator of Tie2. [Aerpio Pharmaceuticals, Inc.] Press Release

Adverum Biotechnologies Doses First Patient in Second Cohort of OPTIC Phase I Clinical Trial of ADVM-022 Gene Therapy for Wet AMD

Adverum Biotechnologies, Inc. announced that the first patient was dosed in the second cohort of the ongoing OPTIC Phase I clinical trial for ADVM-022 for the treatment of wet age-related macular degeneration (AMD). ADVM-022 is designed to provide sustained therapeutic levels of aflibercept, minimize the burden of frequent anti-VEGF injections, and improve real-world vision outcomes for patients with wet AMD. [Adverum Biotechnologies, Inc.] Press Release

Judge Says FDA Can Stop Clinic from Selling Stem Cell Treatments

The decision may facilitate the agency cracking down more effectively on the unproven interventions these companies sell. [The Scientist] Editorial

NIH Has Referred 16 Allegations of Foreign Influence on US Research to Investigators

The National Institutes of Health (NIH) has referred 16 allegations related to foreign influence of US-funded research to investigators and contacted 61 research institutions about such concerns, federal health officials said at a hearing. [STAT News] Editorial

Hungarians Protest against Proposed Government Takeover of Science

Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial

NEW 6^th Annual European Congress on Clinical and Translational Medicine
October 18-20, 2019
Vienna, Austria

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Endothelial Dysfunction in Inflammatory Disease (Seattle Children’s Hospital)

NEW Assistant/Associate Professor – Vascular Physiology & Disease (Stanford Medicine)

Postdoctoral Fellowship – Neurovascular Imaging Research (University of Nevada)

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)

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

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