Endothelial Cell News Volume 5.11 | Mar 30 2020

TOP STORY

Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling

Researchers showed that acute injury and blood-brain barrier disruption triggered the formation of a prominent mitochondrial-enriched compartment in astrocytic endfeet, which enabled vascular remodeling. Integrated imaging approaches revealed that this mitochondrial clustering was part of an adaptive response regulated by fusion dynamics. [Cell Metab] Abstract | Graphical Abstract

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Single-Cell Chromatin Accessibility Maps Reveal Regulatory Programs Driving Early Mouse Organogenesis

Integrated gene expression and transcription factor motif enrichment analyses highlighted cell-type-specific transcriptional regulators. Subsequent in vivo experiments in zebrafish revealed a role for the ETS factor FEV in endothelial identity downstream of ETV2. [Nat Cell Biol] Abstract

Single-Cell Profiling Reveals an Endothelium-Mediated Immunomodulatory Pathway in the Eye Choroid

By combining single-cell and bulk RNA sequencing, investigators categorized mouse retinal pigment epithelium (RPE)/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. They found that choroidal endothelium adjacent to the RPE expressed high levels of Indian Hedgehog and identified its downstream target as stromal GLI1⁺ mesenchymal stem cell-like cells. [J Exp Med] Full Article | Graphical Abstract

Genetic and Structural Studies of RABL3 Reveal an Essential Role in Lymphoid Development and Function

Homozygous knockout alleles of mouse Rabl3 were embryonic lethal, but a viable hypomorphic allele causing in-frame deletion of four amino acids from the interswitch region resulted in profound defects in lymphopoiesis. Impaired lymphoid progenitor development led to deficiencies of B cells, T cells, and natural killer cells in Rabl3^xm/xm mice. [Proc Natl Acad Sci USA] Abstract

Function of Arl4aa in the Initiation of Hematopoiesis in Zebrafish by Maintaining Golgi Complex Integrity in Hemogenic Endothelium

Zebrafish ADP-ribosylation factor-like 4aa arl4aa was preferentially expressed in the ventral wall of the dorsal aorta at 24 and 36 hpf and in caudal hematopoietic tissue at 48 hpf. [Stem Cell Reports] Full Article

Visfatin/eNampt Induces Endothelial Dysfunction In Vivo: A Role for Toll-Like Receptor 4 and NLRP3 Inflammasome

Scientists studied Toll-like receptor-4’s (TLR4’s) capacity to generate vascular dysfunction in vivo, focusing on TLR4 role and downstream activation of nod-like-receptor-protein-3 (NLRP3)-inflammasome. Four month-old C57BL/6 mice were exposed to seven days infusion of visfatin/eNampt, alone or together with FK 866, CLI 095, MCC 950, or anakinra. [Sci Rep] Full Article

Differential Regulation of MicroRNA-15a by Radiation Affects Angiogenesis and Tumor Growth via Modulation of Acid Sphingomyelinase

Mechanistically, inhibition of miR-15a increased inflammatory cytokined, activated caspase-1 inflammasome and increased Gasdermin D, an effector of pyroptosis. Both systemic and vascular-targeted delivery of miR-15a inhibitor decreased angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. [Sci Rep] Full Article

Neutrophil-Derived Exosome from Systemic Sclerosis Inhibits the Proliferation and Migration of Endothelial Cells

Exosomes (EXOs) were isolated from plasma, cultured peripheral blood mononuclear cells/neutrophil supernatants, and identified by transmission electron microscopy. The expression of S100A8/A9 was measured by real-time PCR and ELISA. [Biochem Biophys Res Commun] Abstract

iPSC-Derived Endothelial Cell Response to Hypoxia via Sdf1a/Cxcr4 Axis Facilitates Incorporation to Revascularize Ischemic Retina

To test the therapeutic feasibility of human-induced pluripotent stem cell–derived endothelial cells (hiPSC-ECs) for the treatment of ischemic retinopathies, the authors compared the angiogenic potential of hiPSC-ECs with mature human retinal endothelial cells in response to hypoxia. [JCI Insight] Abstract

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Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. [Int J Mol Sci] Full Article

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Opthea Completes Patient Dosing in Phase IIa DME Trial

Opthea Limited has completed patient dosing and all follow-up week 12 patient visits in the company’s Phase IIa trial evaluating the safety and efficacy of OPT-302 administered in combination with aflibercep for treatment of diabetic macular edema (DME). [Opthea Limited] Press Release

UD’s Jason Gleghorn Receives NSF Career Award

The University of Delaware’s (UD’s) Jason Gleghorn, an assistant professor in biomedical engineering with a joint appointment in biological sciences, has received a National Science Foundation (NSF) Faculty Early Career Development Award to understand how the body’s adaptive immune system activates. [The University of Delaware] Press Release

Tens of Thousands of Scientists Are Redeploying to Fight Coronavirus

As labs shut down around the world, researchers are finding creative ways to donate their time, supplies and expertise. [Nature News] Editorial

Universities Issue Hiring Freezes in Response to COVID-19

Numerous universities have made announcements about the suspension of hiring, including Miami University of Ohio, Wright State University, Villanova University, the University of Nevada, Reno, Indiana University, and the University of Auckland in New Zealand, which cites the travel ban affecting Chinese students as one of the main causes of its freeze. [The Scientist] Editorial

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NEW Project Manager – Cardiovascular Clinical Trials (Cardiovascular Research Foundation)

Postdoctoral Research Fellow – Molecular Oncology (Genentech, Inc.)

Postdoctoral Scientist – Gene Editing in Liver Disease (Beam Therapeutics)

Research Assistant – VEGF and Immune Response (Case Western Reserve University)

Senior Research Associate – In Vitro Disease Models (Kodiak Sciences)

Research Fellow – Cardiovascular Disease (Queen’s University Belfast)

Postdoctoral Researcher – Endothelial Mechanotransduction (KU Leuven)

Postdoctoral Researchers – Pancreatic-Endothelial Cell Interactions (German Research Center for Environmental Health)

Career Scientist – Neurosurgery and Regenerative Medicine (Mayo Clinic)

Postdoctoral Researcher – Neurodegeneration and Vascular Functions (Icahn School of Medicine at Mount Sinai)

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