Endothelial Cell News Volume 3.23 | Jul 9 2018

TOP STORY

Single-Cell Analysis of Early Progenitor Cells That Build Coronary Arteries

Using single-cell RNA sequencing and mouse genetics, investigators showed that vein cells of the developing heart undergo an early cell fate switch to create a pre-artery population that subsequently builds coronary arteries. [Nature] Abstract

(Ranked by impact factor of the journal)

SMAD4 Prevents Flow Induced Arterial-Venous Malformations by Inhibiting Casein Kinase 2

Scientists found that loss of endothelial Smad4 resulted in arterial-venous malformation (AVM) and lethality. Smad4^iΔEC endothelial cells in AVMs displayed increased PI3K/AKT signaling, and pharmacological PI3K inhibitors or endothelial Akt1 deletion both rescued AVM formation in Smad4^iΔEC mice. [Circulation] Abstract

Reversal of Endothelial Dysfunction Reduces White Matter Vulnerability in Cerebral Small Vessel Disease in Rats

In a rat model of small vessel disease (SVD), investigators showed that endothelial cell (EC) dysfunction is the first change in development of the disease. Dysfunctional ECs secreted heat shock protein 90α, which blocked oligodendroglial differentiation, contributing to impaired myelination. Treatment with EC-stabilizing drugs reversed these EC and oligodendroglial pathologies in the rat model. [Sci Transl Med] Abstract | Press Release

miR-103 Promotes Endothelial Maladaptation by Targeting lncWDR59

Researchers showed that hyperlipidemia- and oxLDL-induced upregulation of miR-103 inhibits endothelial cell proliferation and promotes endothelial DNA damage through targeting of novel lncWDR59. [Nat Commun] Full Article

Intermedin Protects against Sepsis by Concurrently Re-Establishing the Endothelial Barrier and Alleviating Inflammatory Responses

Scientists showed that intermedin (IMD), a member of the calcitonin family, alleviates organ injury and decreases mortality in septic mice by concurrently alleviating vascular leakage and inflammatory responses. IMD promoted the relocation of vascular endothelial cadherin through a Rab11-dependent pathway to dynamically repair the disrupted endothelial junction. [Nat Commun] Full Article

Serum Exosomes Mediate Delivery of Arginase 1 as a Novel Mechanism for Endothelial Dysfunction in Diabetes

Reseachers showed that serum exosomes (SExos) from diabetic db/db mice were taken up by aortic endothelial cells, which severely impaired endothelial function in nondiabetic db/m⁺ mice. [Proc Natl Acad Sci USA] Abstract

FOXP3 Inhibits Angiogenesis by Downregulating VEGF in Breast Cancer

Investigators found that the clinical expression of nuclear forkhead box P3 (FOXP3) was inversely correlated with breast cancer angiogenesis. Moreover, the animal study demonstrated that FOXP3 significantly reduced the microvascular density of MDA-MB-231 tumors transplanted in mice. [Cell Death Dis] Full Article

Different Concentrations of Lipopolysaccharide Regulate Barrier Function through the PI3K/Akt Signaling Pathway in Human Pulmonary Microvascular Endothelial Cells

Low doses of lipopolysaccharides increased human pulmonary microvascular endothelial cell migration, up-regulated VE-cadherin and claudin-5 expression, down-regulated Connexin-43 expression, and promoted Akt phosphorylation, which could collectively decrease monolayer permeability. [Sci Rep] Full Article

Expression of Periaxin (PRX) Specifically in the Human Cerebrovascular System: PDZ Domain-Mediated Strengthening of Endothelial Barrier Function

The authors discovered that the PDZ-domain containing protein periaxin (PRX) is expressed in human cerebral endothelial cells. Surprisingly, PRX protein was not detected in brain endothelium in other mammalian species, suggesting that it could confer human-specific vascular properties. [Sci Rep] Full Article

Improved Vasculogenesis and Bone Matrix Formation through Co‐Culture of Endothelial Cells and Stem Cells in Tissue‐Specific Methacryloyl Gelatin‐Based Hydrogels

A co‐culture system combining primary human adipose‐derived stem cells and primary human dermal microvascular endothelial cells within two types of hydrogels based on methacryl‐modified gelatin as 3D scaffolds was examined regarding its support of tissue specific cell functions. [Biotechnol Bioeng] Abstract

ClC-3 Promotes Angiotensin II-Induced Reactive Oxygen Species Production in Endothelial Cells by Facilitating Nox2 NADPH Oxidase Complex Formation

Researchers investigated the effects and mechanisms of ClC-3 on NADPH oxidase activation and reactive oxygen species generation in endothelial cells. Treatment with angiotensin II significantly elevated ClC-3 expression in cultured HUVECs. [Acta Pharmacol Sin] Abstract

Induced Pluripotent Stem Cell-Derived Endothelial Cells Promote Angiogenesis and Accelerate Wound Closure in a Murine Excisional Wound Healing Model

The authors used a murine excisional wound model to test the pro-angiogenic properties of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) in wound healing. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. [Biosci Rep] Abstract | Full Article

Endothelial siRNA Delivery in Nonhuman Primates Using Ionizable Low-Molecular Weight Polymeric Nanoparticles

Toward the goal of creating a new RNA-based therapy to correct aberrant endothelial cell gene expression in humans, efficient gene silencing in the endothelium of nonhuman primates was achieved by delivering small interfering RNA (siRNA) with 7C1, a low–molecular weight, ionizable polymer that forms nanoparticles. [Sci Adv] Full Article

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The Vascularised Chamber as an In Vivo Bioreactor

The authors outline the chamber concept and explore its application in the context of recent advances in biomedical engineering, and how this can play a role in the future of cell therapies and regenerative medicine. [Trends Biotechnol] Abstract

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

UH Cancer Center Renews NCI Designation

The University of Hawai‘i (UH) Cancer Center successfully competed for renewal of National Cancer Institute (NCI) designation, and has been awarded a $6 million Cancer Center Support Grant to fund research at the Center. [University of Hawai’i Cancer Center] Press Release

Opthea’s Phase IIb Wet AMD Clinical Trial Reaches Mid-Way Point of Patient Recruitment

Opthea Limited announced it has reached the mid-way point of patient recruitment for its Phase IIb clinical trial of OPT-302 in wet age-related macular degeneration patients. OPT-302 is a soluble form of VEGFR-3 or ‘Trap’ molecule that blocks the activity of two proteins (VEGF-C and VEGF-D) that cause blood vessels to grow and leak, processes which contribute to the pathophysiology of retinal diseases. [Opthea Limited (GlobeNewswire, Inc.)] Press Release

Controversial CRISPR ‘Gene Drives’ Tested in Mammals for the First Time

A controversial technology capable of altering the genomes of entire species has been applied to mammals for the first time. In a preprint posted to bioRxiv on 4 July, researchers describe developing ‘gene drives’ — which could be used to eradicate problematic animal populations — in lab mice using the CRISPR gene-editing technique. [Nature News] Editorial

China’s Scientific Revolution

The country is making a serious investment in becoming a world-class science superpower. [Scientific American] Editorial

Hidden Conflicts? Pharma Payments to FDA Advisers after Drug Approvals Spark Ethical Concerns

In examining compensation records from drug companies to physicians who advised FDA on whether to approve 28 psychopharmacologic, arthritis, and cardiac or renal drugs between 2008 and 2014, Science found widespread after-the-fact payments or research support to panel members. The agency’s safeguards against potential conflicts of interest are not designed to prevent such future financial ties. [ScienceInsider] Editorial

Hungarian Academy to Draw Up Alternative Research Budget

The Hungarian Academy of Sciences is set to put forward an “alternative proposal” for the country’s research budget, after the government moved to put the Ministry of Innovation and Technology in charge of financing research institutions, seen as the latest attack on sector autonomy by the authoritarian Orbán administration. [Times Higher Education] Editorial

NEW The American Society for Cell Biology (ASCB) Annual Meeting 2018
December 8-12, 2018
San Diego, California, United States

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

NEW Postdoctoral Position – Cancer Metabolism by Blood Vessels (German Cancer Research Center)

NEW Research Associate – Embryonic Stem Cell Derivatives for Vascular Grafts (Imperial College London)

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

Postdoctoral Associate – Biomedical Engineering (University of Minnesota)

Research Technologist – Endothelial Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Vascular and Endothelial Cell Biology (Augusta University)

Postdoctoral Position – Vascular Development (University of Massachusetts)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University)

Postdoctoral Researcher – Immunotherapy (Memorial Sloan Kettering Cancer Center)

Postdoctoral Fellow – Endothelial Cell Biology (Blood Research Institute)

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