Endothelial Cell News Volume 4.18 | May 27 2019

TOP STORY

ZFYVE21 Is a Complement-Induced Rab5 Effector That Activates Non-Canonical NF-κB via Phosphoinosotide Remodeling of Endosomes

Scientists identified ZFYVE21 as a complement-induced Rab5 effector that induced non-canonical NF-κB in endothelial cells. In response to membrane attack complexes (MAC), ZFYVE21 was post-translationally stabilized on MAC⁺Rab5⁺ endosomes in a Rab5- and PI(3)P-dependent manner. [Nat Commun] Full Article

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Paraxial Mesoderm Is the Major Source of Lymphatic Endothelium

Investigators showed that paraxial mesoderm (PXM)-derived cells formed the lymphatic endothelium of multiple organs and tissues, with a more restricted contribution to blood vessel endothelium. By deleting Prox1 specifically in PXM-derived cells, they showed that this lineage was indispensable for lymphatic vessel development. [Dev Cell] Full Article | Graphical Abstract

Angiogenic Factor AGGF1-Primed Endothelial Progenitor Cells Repair Vascular Defect in Diabetic Mice

The authors showed that endothelial progenitor cells (EPCs) from heterozygous knockout Aggf1^+/- mice showed impairment of proliferation, migration, angiogenesis, and transendothelial migration as in hyperglycemic mice fed with a high fat diet or db/db mice. Ex vivo, the AGGF1 protein could fully reverse all the damaging effects of hyperglycemia on EPCs. [Diabetes] Abstract

Characterization of P2Y₂ Receptors in Human Vascular Endothelial Cells Using AR-C118925XX, a Competitive and Selective P2Y₂ Antagonist

Researchers characterized the pharmacological properties of the proposed P2Y₂ receptor antagonist, AR-C118925XX, and then used it to determine the role of P2Y₂ receptors in the action of the P2Y₂ agonist, UTP, in human vascular endothelial cells. [Br J Pharmacol] Abstract

Histidine-Rich Glycoprotein Ameliorates Endothelial Barrier Dysfunction through Regulation of NF-κB and MAPK Signal Pathway

Investigators showed that histidine-rich glycoprotein (HRG) maintained endothelial monolayer integrity by inhibiting cytoskeleton reorganization, loss of VE-cadherin and β-catenin, focal adhesion kinase degradation and cell detachment induced by LPS/TNF-α. HRG also inhibited cytokine secretion from endothelial cells induced by LPS/TNF-α, which was associated with reduced NF-κB activation. [Br J Pharmacol] Abstract

MicroRNA-615-5p Regulates Angiogenesis and Tissue Repair by Targeting AKT/eNOS (Endothelial NO Synthase) Signaling in Endothelial Cells

Ectopic expression of miR-615-5p markedly inhibited endothelial cell proliferation, migration, network tube formation in Matrigel, and the release of nitric oxide, whereas miR-615-5p neutralization had the opposite effects. Scientists demonstrated that miR-615-5p inhibited the VEGF-AKT/eNOS signaling pathway in endothelial cells by targeting insulin-like growth factor 2 and Ras-associating domain family member 2. [Arterioscler Thromb Vasc Biol] Abstract | Full Article

Vitamin D Improves Endothelial Barrier Integrity and Counteracts Inflammatory Effects on Endothelial Progenitor Cells

Researchers investigated endothelial barrier characteristics of endothelial colony-forming cells (ECFCs), whether vitamin D supports cell-cell adhesion and barrier integrity, and how it affects ECFC mobilization and actin dynamics. Although the ECFC barrier was disrupted under inflammatory conditions, this effect was rescued by vitamin D treatment, leading to higher stability of an ECFC monolayer. Furthermore, vitamin D enhanced ECFC mobilization toward directional migration. [FASEB J] Abstract

Time-Variant SRC Kinase Activation Determines Endothelial Permeability Response

Investigators discovered that the immediate effect of SRC activation was to transiently enhance endothelial barrier function as the result of accumulation of VE cadherin at adherens junctions (AJs) and formation of morphologically distinct reticular AJs. Endothelial barrier enhancement via SRC required phosphorylation of VE cadherin at Y731. In contrast, prolonged SRC activation induced VE cadherin phosphorylation at Y685, resulting in increased endothelial permeability. [Cell Chem Biol] Abstract | Graphical Abstract

Human Embryonic Stem Cell-Derived Exosomes Promote Pressure Ulcer Healing in Aged Mice by Rejuvenating Senescent Endothelial Cells

In vitro, exosomes from human embryonic stem cells (ESC-Exos) could rejuvenate senescence of endothelial cells and recover compromised proliferation, migratory capacity, and tube formation. This recovery was Nrf2-activation-dependent, since cotreatment with Nrf2 inhibitor Brusatol could abolish the rejuvenative effects of ESC-Exos. [Stem Cell Res Ther] Full Article

Dickkopf-1 Treatment Stimulates Hematopoietic Regenerative Function in Infused Endothelial Progenitor Cells

To understand how dickkopf1 (Dkk1) induced regenerative function in the endothelial progenitor cells (EPCs), researchers screened for pro-regenerative factors secreted by the EPC in response to Dkk1. Dkk1-treated EPCs were observed to secrete high levels of the anti-fibrotic protein follistatin as well as several proteins known to promote regeneration including EGF, VEGF and G-CSF. [Radiat Res] Abstract

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Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology

The authors summarize the activity of angiopoietin-2 in blood and lymphatic endothelial cells, its different functions in the body under both physiological and pathological conditions, and the main molecular mechanisms identified to date. [Cells] Full Article

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Opthea Completes Final Patient Visit in Phase IIb Wet AMD Clinical Trial

Opthea Limited announced that the final patient in the company’s Phase IIb trial of OPT-302 for wet age-related macular degeneration (AMD) has completed their last clinical visit. OPT-302 is a soluble form of VEGF receptor 3 or ‘Trap’ molecule that blocks the activity of two proteins that cause blood vessels to grow and leak, processes which contribute to the pathophysiology of retinal diseases. [Opthea Limited] Press Release

$12.5 Million Grant Funds Ambitious Health Research Collaboration

A groundbreaking research collaboration that is shedding light on everything from cancer to diabetes to cardiovascular disease has received $12.5 million from the National Institutes of Health. The grant funding from the National Heart, Lung and Blood Institute will support the next five years of research for an initiative that is unusual both in its focus and its approach. [University of Virginia Health System] Press Release

Case Comprehensive Cancer Center Awarded Nearly $9 Million to Expand Access to Clinical Trials

Case Comprehensive Cancer Center has been selected, once again, as a Lead Academic Participating Site by the National Cancer Institute. The renewal comes with a six-year, $8.9 million grant that will enable the center to provide patients with additional access to clinical trials through the National Clinical Trials Network. [Case Western Reserve University] Press Release

Taiwan Considers Double-Blind Peer Review for Grants

Taiwan’s science ministry is thinking of introducing double-blind peer review to assess research-grant proposals, a trend being adopted by some journals to eliminate bias. [Nature News] Editorial

Brazilian Scientists Strive to Turn Politicians into Allies

Brazil’s scientists are fighting back against President Jair Bolsonaro’s plans to slash funding for research and education programs. Researchers have joined with members of Brazil’s legislature, the National Congress, to highlight the strategic role that science, technology, and education play in the country’s economic and social development. [Nature News] Editorial

Emory Ousts Two Chinese-American Researchers after Investigation into Foreign Ties

Emory University has ousted two veteran biomedical researchers and shuttered their laboratory after the National Institutes of Health expressed concern about their foreign ties. The researchers “had failed to fully disclose foreign sources of research funding and the extent of their work for research institutions and universities in China,” the Atlanta-based university said in a statement first reported today by The Atlanta Journal-Constitution. [ScienceInsider] Editorial

NEW Organoids Are Us 2019
June 25, 2019
Parkville, Australia

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

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

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

NEW 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)

Postdoctoral Scientists – Metabolic Regulation of Vascular Formation (Oklahoma Medical Research Foundation)

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

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