Endothelial Cell News Volume 4.22 | Jun 24 2019

TOP STORY

15-Deoxy-Δ12,14-Prostaglandin J2 Reinforces the Anti-Inflammatory Capacity of Endothelial Cells with a Genetically Determined Nitric Oxide Deficit

Exposure of human endothelial cells (ECs) to fluid shear stress (FSS) effectively reduced monocyte transmigration particularly through monolayers of CC-genotype ECs. Primarily in CC-genotype ECs, FSS elicited a marked rise in cyclooxygenase-2 and lipocalin-type prostaglandin D synthase expression, which appeared to be nitric oxide-sensitive, and provoked a significant release of 15-deoxy-Δ12,14-prostaglandin J2 over baseline. [Circ Res] Abstract

(Ranked by impact factor of the journal)

Endothelial Cell Clonal Expansion in the Development of Cerebral Cavernous Malformations

Researchers showed that cavernomas originated from clonal expansion of few cerebral cavernous malformation 3-null endothelial cells that expressed mesenchymal/stem-cell markers. These cells attracted surrounding wild-type endothelial cells, inducing them to express mesenchymal/stem-cell markers and to contribute to cavernoma growth. [Nat Commun] Full Article

Cerebrovascular Endothelial Cells Form Transient Notch-Dependent Cystic Structures in Zebrafish

Scientists identified a novel endothelial membrane behavior in transgenic zebrafish. Cerebral blood vessels extruded large transient spherical structures that persisted for an average of 23 minutes before regressing into the parent vessel. They termed these structures “kugeln”. Kugeln did not interact with brain lymphatic endothelial cells and could form in their absence, nor did they perform a scavenging role or interact with macrophages. [EMBO Rep] Abstract | Graphical Abstract

Hemogenic Endothelial Cells Can Transition to Hematopoietic Stem Cells through a B-1 Lymphocyte-Biased State during Maturation in the Mouse Embryo

Investigators found that freshly isolated CD45⁻VE-cadherin⁺KIT⁺ cells exhibited significantly greater B-1 lymphocyte-biased repopulating capacity than multilineage repopulating capacity. They demonstrated the predominant B-1 progenitor colony-forming ability of these cells; however, increased B-2 progenitor colony-forming ability emerged after co-culture with Akt-expressing aorta-gonad-mesonephros endothelial cells, conditions that supported pre-hematopoietic stem cell (HSC) maturation into HSCs. [Stem Cell Reports] Full Article | Graphical Abstract

Microglia-Derived TNF-α Mediates Endothelial Necroptosis Aggravating Blood Brain-Barrier Disruption after Ischemic Stroke

The authors showed that perivascular M1-like microglia-induced endothelial necroptosis leading to blood-brain barrier (BBB) disruption required tumor necrosis factor-α (TNF-α) secreted by M1 type microglia and its receptor, TNF receptor 1, on endothelium as the primary mediators of these effects. Anti-TNFα treatment significantly ameliorated endothelial necroptosis, BBB destruction and improved stroke outcomes. [Cell Death Dis] Full Article

Single and Fractionated Ionizing Radiation Induce Alterations in Endothelial Connexin Expression and Channel Function

Researchers investigated the consequences of endothelial cell irradiation on connexin (Cx) expression and channel function. Telomerase immortalized human coronary artery/microvascular endothelial cells were exposed to single and fractionated X-rays. Several biological endpoints were investigated at different time points after exposure: Cx gene and protein expression, gap junctional dye coupling and hemichannel function. [Sci Rep] Full Article

Endothelial Cells Promote 3D Invasion of GBM by IL-8-Dependent Induction of Cancer Stem Cell Properties

To simulate perivascular niche conditions and analyze consequential changes of glioblastoma (GBM) growth and invasion, patient-derived GBM spheroids were co-cultured with brain endothelial cells (ECs) in microfabricated collagen gels. Integrating these systems with 3D imaging and biochemical assays revealed that ECs increased GBM invasiveness and growth through interleukin-8 (IL-8)-mediated enrichment of cancer stem-like cells. [Sci Rep] Full Article

Silencing of PTGS2 Exerts Promoting Effects on Angiogenesis Endothelial Progenitor Cells in Mice with Ischemic Stroke via Repression of the NF-κB Signaling Pathway

Scientists investigated the effect of PTGS2 on proliferation, migration, angiogenesis and apoptosis of endothelial progenitor cells (EPCs) in mice with ischemic stroke through the NF-κB signaling pathway. Middle cerebral artery occlusion model was established in mice. EPCs were identified, in which ectopic expression and depletion experiments were conducted. [J Cell Physiol] Abstract

The Pregnane X Receptor and Its Microbiota-Derived Ligand, Indole 3-Propionic Acid, Regulate Endothelium-Dependent Vasodilation

Indole 3-propionic acid (IPA) exposure reduced the vasodilatory responses in isolated and cultured vessels. No effects of IPA were observed for tissues obtained from pregnane X receptor (Pxr)^-/- mice. Serum nitrate levels were increased in antibiotic-treated Pxr^+/+ and Pxr^-/- mice. Endothelial nitric oxide synthase abundance was increased in aorta tissues and cultured endothelium from Pxr^-/- mice. [Am J Physiol Endocrinol Metab] Abstract

Pyrroloquinoline Quinine Ameliorates Doxorubicin-Induced Autophagy-Dependent Apoptosis via Lysosomal-Mitochondrial Axis in Vascular Endothelial Cells

Investigators found that treatment of HUVECs with doxorubicin (DOX) induced autophagy and apoptosis in a dose- and time-dependent manner. Treatment with DOX induced autophagy at an earlier time, then lysosomal membrane permeabilization altered after treatment for 12 hours which was followed by the release of cathepsin D. Lysosome-associated membrane proteins-1 and -2 were decreased in DOX-treated cells. [Toxicology] Abstract

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Local Pharmacological Induction of Angiogenesis: Drugs for Cells and Cells as Drugs

The authors review three strategies to achieve (neo)angiogenesis in ischemic tissue with focus on the angiogenic mechanisms they tackle, such as transcription cascades, specific signaling steps and cellular gases. They also include cancer-therapy relevant lymphangiogenesis, and seek to explain why there are often conflicting data between in vitro and in vivo. [Adv Drug Deliv Rev] Abstract | Graphical Abstract

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

Asieris Announces Completion of Enrollment for Its US APL-1202 Phase Ib Clinical Trial

Asieris announced the completion of enrollment for its APL-1202 Phase Ib trial in the US. This new drug is being developed for the treatment of non-muscle invasive bladder cancer. APL-1202 is the first oral and reversible methionine aminopeptidase II type inhibitor under clinical development in the world. It has novel mechanisms of action of inhibiting both tumor cell growth and angiogenesis. [Asieris (PR Newswire Association LLC)] Press Release

Chan Zuckerberg Initiative Awards $68 Million to Support the Growth of the Human Cell Atlas

The Chan Zuckerberg Initiative (CZI) announced $68 million in funding to support the Human Cell Atlas and its selection of 38 collaborative science teams to launch CZI’s Seed Networks for a Human Cell Atlas projects. These collaborative groups bring together scientists, computational biologists, software engineers, and physicians to support the continued development of the Human Cell Atlas, an international effort to map all cells in the human body. [The Chan Zuckerberg Initiative] Press Release

Iranian Biologists Face US Trial for Trying to Take Proteins Out of the Country

Three Iranian biologists are facing trial in a US court over charges that they violated trade sanctions by attempting to export chemicals known as growth factors, which are commonly used in medical research. The scientists have asked a federal district court judge in Atlanta, Georgia, to dismiss the criminal charges against them. [Nature News] Editorial

UK’s Leading Mouse Genetics Center Faces Closure

Britain’s leading center for mouse genetics is facing closure in a move that critics say will undermine crucial research on serious diseases and threaten the standing of UK science. The Medical Research Council has told staff at its Harwell Institute in Oxfordshire that an internal strategy board recommended the closure of all academic work at the site, threatening research on diabetes, neurodegenerative disease, child deafness and other conditions. [The Guardian] Editorial

House Panel Clarifies How Universities Would Report Sexual Harassment Cases to US Funders

New rules from the National Science Foundation (NSF) on reporting sexual harassment by someone with an NSF grant raise questions about due process, university administrators say. A key congressional panel took those concerns to heart by modifying language in a bill that would require the administration to write guidelines applying to half a dozen major federal research agencies. [ScienceInsider] Editorial

NEW Cell Symposia: Gene and Cell Based Therapies: CRISPR, Stem Cells & Beyond
March 2-4, 2020
San Francisco, California, United States

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NEW Postdoctoral Position – Vascular Research (University of Illinois-Chicago)

Faculty Positions – Cardiovascular Biomedical Research (Virginia Tech)

PhD Position – Vascular Biology (Karolinska Institutet)

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

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

Postdoctoral Fellowship – Neurovascular Imaging Research (University of Nevada)

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)

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

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