Endothelial Cell News Volume 4.02 | Jan 21 2019

TOP STORY

Human Blood Vessel Organoids as a Model of Diabetic Vasculopathy

Scientists report the development of self-organizing 3-D human blood vessel organoids from pluripotent stem cells. These human blood vessel organoids contained endothelial cells and pericytes that self-assembled into capillary networks that are enveloped by a basement membrane. Human blood vessel organoids transplanted into mice formed a stable, perfused vascular tree, including arteries, arterioles and venules. [Nature] Abstract | Press Release 1 | Press Release 2

(Ranked by impact factor of the journal)

FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration

FOXO3-activated vascular cells exhibited delayed aging and increased resistance to oxidative injury compared with wild-type cells. When tested in a therapeutic context, FOXO3-enhanced vascular cells promoted vascular regeneration in a mouse model of ischemic injury and were resistant to tumorigenic transformation both in vitro and in vivo. [Cell Stem Cell] Abstract | Graphical Abstract

Microvascular Endothelial Cells Engulf Myelin Debris and Promote Macrophage Recruitment and Fibrosis after Neural Injury

Researchers showed that endothelial cells exerted critical functions beyond myelin clearance to promote progression of demyelination disorders by regulating macrophage infiltration, pathologic angiogenesis and fibrosis in both spinal cord injury and experimental autoimmune encephalomyelitis. [Nat Neurosci] Abstract | Press Release

Metformin Alleviates Hyperglycemia-Induced Endothelial Impairment by Downregulating Autophagy via the Hedgehog Pathway

db/db mice were treated with intravitreal metformin injections. HUVECs were cultured either in normal glucose or high glucose medium in the presence or absence of metformin for 72 hours. Deletion of ATG7 in retinal vascular endothelial cells of db/db mice and cultured HUVECs indicated a detrimental role of autophagy in hyperglycemia-induced endothelial dysfunction. [Autophagy] Abstract

TAK1 Prevents Endothelial Apoptosis and Maintains Vascular Integrity

The authors showed that TGF-β-activated kinase 1 (TAK1) ensured endothelial cell (EC) survival and maintained vascular integrity upon TNF-α stimulation. Endothelial-specific TAK1 knockout mice exhibited intestinal and liver hemorrhage due to EC apoptosis, leading to vascular destruction and rapid death. [Dev Cell] Full Article | Press Release | Graphical Abstract

Sema3E/PlexinD1 Signaling Inhibits Postischemic Angiogenesis by Regulating Endothelial DLL4 and Filopodia Formation in a Rat Model of Ischemic Stroke

At the microcosmic level, semaphorin 3E (Sema3E)/PlexinD1 signaling promoted F-actin disassembly and focal adhesion reduction by activating the small guanosine triphosphatase Ras homolog family member J by releasing RhoGEF Tuba from direct binding to PlexinD1, thus mediating endothelial cell motility and filopodia retraction. [FASEB J] Abstract

Sphingosine-1-Phosphate Promotes Barrier-Stabilizing Effects in Human Microvascular Endothelial Cells via AMPK-Dependent Mechanisms

Sphingosine-1-phosphate enhanced the basal endothelial barrier in human microvascular endothelial cells (HMEC-1) exclusively. siRNA-mediated knockdown of AMP-dependent kinase (AMPK) in HMEC-1 led to a less pronounced barrier enhancement. [BBA-Mol Basis Dis] Full Article | Graphical Abstract

OxHDL Controls LOX-1 Expression and Plasma Membrane Localization through a Mechanism Dependent on NOX/ROS/NF-κB Pathway on Endothelial Cells

Investigators demonstrated that the incubation of arterial or vein endothelial cells with oxidation of circulating high-density lipoprotein (oxHDL) induced the increase of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression at the plasma membrane; effect prevented by LOX-1 inhibition. The same results were observed in endothelial cells from oxHDL-treated rats. [Lab Invest] Abstract

Synaptotagmin 5 Regulates Calcium-Dependent Weibel-Palade Body Exocytosis in Human Endothelial Cells

Western blot analysis of HUVECs identified the synaptotagmin 5 (SYT5) protein, and exogenously expressed SYT5-mEGFP localized almost exclusively to Weibel-Palade bodies (WPBs). shRNA-mediated knockdown of endogenous SYT5 reduced the rate and extent of histamine-evoked WPB exocytosis and reduced secretion of the WPB cargo Von Willebrand factor-propeptide. [J Cell Sci] Abstract

Impairment of Hypoxia-Induced Angiogenesis by LDL Involves a HIF-Centered Signaling Network Linking Inflammatory TNFα and Angiogenic VEGF

Low-density lipoprotein (LDL) prevented expression of hypoxia inducible factors (HIFs) in endothelial cells (ECs) exposed to either hypoxia or TNFα, while knockdown of either HIF-1α or HIF-2α strikingly attenuated hypoxia-induced production of VEGF by ECs as well as EC colony formation and tube formation. [Aging (Albany NY)] Full Article

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Acid Ceramidase, an Emerging Target for Anti-Cancer and Anti-Angiogenesis

The equilibrium in ceramide and sphingosine-1-phosphate levels in cells plays an important role in angiogenesis as well as cell death. Acid ceramidase is a promising target protein in the development of multi-targeted anticancer drugs as its inhibition can simultaneously inhibit angiogenesis via the Akt and ERK 1/2 pathway and limit cancer growth through ceramide-induced apoptosis. [Arch Pharm Res] Abstract

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Aerpio Pharmaceuticals Announces Completion of Patient Dosing in TIME-2b Study of AKB-9778 in Diabetic Retinopathy

Aerpio Pharmaceuticals, Inc. announced the completion of patient dosing in the company’s TIME-2b study, a Phase IIb clinical trial designed to assess the efficacy and safety of Aerpio’s lead candidate, AKB-9778, for patients with moderate to severe non-proliferative diabetic retinopathy. AKB-9778 binds to and inhibits vascular endothelial protein tyrosine phosphatase, an important negative regulator of Tie2. [Aerpio Pharmaceuticals, Inc.] Press Release

FDA Planning New Guidance, Hires in Cell and Gene Therapies for 2019

The FDA plans to hire at least 50 new clinical reviewers tasked with assessing cell and gene therapies to prepare for what the agency describes as a surge of cutting-edge products currently entering early development. [U.S. Food and Drug Administration (Questex LLC.)] Press Release

Surprise! Shutdown also Disrupting U.S. Science Agencies that Aren’t Closed

Many U.S. government scientists and federally funded researchers breathed a sigh of relief last month, after the partial shutdown of the U.S. government began. That’s because the budget impasse between Congress and President Donald Trump didn’t affect some of the largest federal research agencies, including the $39 billion National Institutes of Health and the $35.6 billion Department of Energy. Their spending had already been approved. [ScienceInsider] Editorial

How UK Scientists Are Planning for a Chaotic No-Deal Brexit

British scientists are ramping up preparations for a ‘no deal’ Brexit on 29 March — a situation that would instantly affect travel, data collection, clinical trials and crucial laboratory supplies. [Nature News] Editorial

German Institutions and Wiley Reach Open-Access Publishing Deal

Ater nearly three years of contract negotiations, a consortium of nearly 700 German libraries, research institutes, and universities called Project DEAL has forged an agreement with the scholarly publisher Wiley that moves the publishing industry towards more open access. [The Scientist] Editorial

NEW Gordon Research Conference: Molecular & Cellular Dynamics of Endothelial Cells in Health & Disease
August 3-4, 2019
Newport, Rhode Island, United States

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NEW Postdoctoral Research Assistant – Endotheial Heterogeneity (University of Oxford)

Postdoctoral Fellows – Vascular Immunology & Immunotherapy (Uppsala University)

Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine)

Assistant Professor Tenure Track – Epithelial Cell Biology (Boston Children’s Hospital)

Postdoctoral Fellowship – Vascular & Valvular Biology (Yale University School of Medicine)

Postdoctoral Fellowship – Cardiovascular Sciences (Medical College of Wisconsin)

Tenure Track Faculty Position – Department of Cancer Biology (KUMC)

Postdoctoral Fellow – Zebrafish Vascular Biology (NYU Langone Medical Center)

Postdoctoral Position – Molecular Neurobiology (San Raffaele Scientific Institute)

Senior Research Assistant – Genitourinary Medical Oncology (MD Anderson Cancer Center)

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

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