Endothelial Cell News Volume 2.03 | Jan 30 2017

TOP STORY

New Peptide Could Improve Treatment for Vision-Threatening Disease

Researchers report that a new peptide holds promise for improving treatment for degenerative retinal diseases, such as age-related macular degeneration, diabetic macular edema and diabetic retinopathy. They showed that the injectable peptide may more strongly suppress abnormal blood vessel growth and leakage in the eye, cause regression of established abnormal vessels, and may last longer when compared to current treatments. [Press release from the Johns Hopkins University discussing online prepublication in Sci Transl Med] Press Release | Abstract

(Ranked by impact factor of the journal)

Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress

Researchers determined the relative importance of transcellular vs. paracellular transport pathways by lymphatic endothelial cells, and how mechanical stress (i.e., fluid flow conditioning) alters either pathway. [Circ Res] Abstract

Lipid Droplet Biogenesis and Function in the Endothelium

Investigators characterized lipid droplet (LD) formation and function in endothelial cells (EC). LD formed and degraded in EC in vivo after fatty acids (FA) loading. In cultured EC, LD synthesis and turnover was dynamic and functioned to protect EC from lipotoxic stress and provided FA for metabolic needs. [Circ Res] Abstract

CAGW Peptide- and PEG-Modified Gene Carrier for Selective Gene Delivery and Promotion of Angiogenesis in HUVECs In Vivo

The authors synthesized the CAGW peptide- and poly(ethylene glycol) (PEG)-modified amphiphilic copolymers. These CAG- and PEG-modified copolymers could form nanoparticles (NPs) by self-assembly method and were used as gene carriers for the pEGFP-ZNF580 (pZNF580) plasmid. CAGW and PEG modification coordinately improved the hemocompatibility and cytocompatibility of NPs. The results of cellular uptake showed significantly enhanced internalization efficiency of pZNF580 after CAGW modification. [ACS Appl Mater Interfaces] Abstract | Graphical Abstract

Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids

Scientists investigated the influence of two bioactive oxidized phospholipids on model bilayer properties, membrane packing, and endothelial cell biomechanics computationally and experimentally. [Biophys J] Abstract

Mitochondrial Connexin40 Regulates Mitochondrial Calcium Uptake in Coronary Endothelial Cells

Scientists observed in coronary endothelial cells (ECs) that the connexin (Cx)40 protein was expressed in the mitochondria, as determined by Western blot and immunofluorescence studies. They found that mouse coronary ECs (MCECs) isolated from Cx40 knockout mice exhibited significantly lower resting mitochondrial calcium concentration than MCECs from wild-type mice. [Am J Physiol Cell Physiol] Abstract

NFAT Regulation of Cystathionine Gamma Lyase Expression in Endothelial Cells is Impaired in Rats Exposed to Intermittent Hypoxia

The authors hypothesized that intermittent hypoxia (IH) exposure reduces [Ca²⁺] activation of calcineurin/NFAT to lower cystathionine gamma lyase expression and impairs vasodilation. They found that in male rats exposed to sham or IH conditions for two weeks, [Ca²⁺] in endothelial cells (EC) in small mesenteric arteries from IH rats was lower than in EC from sham rat arteries and fewer EC were NFATc3 nuclear-positive in IH rat arteries than in sham rat arteries. [Am J Physiol Heart Circ Physiol] Abstract

Constitutive Expression of the Anti-Apoptotic Bcl-2 Family Member A1 in Murine Endothelial Cells Leads to Transplant Tolerance

Investigators created mice expressing murine A1, a Bcl-2 family member, under the control of the human ICAM-2 promoter. Constitutive expression of A1 in murine vascular endothelial cells conferred protection from cell death induced by the pro-inflammatory cytokine TNF-α. Importantly, in a mouse model of heart allograft transplantation, expression of A1 in vascular endothelium increased survival in the absence of CD8⁺ T cells. [Clin Exp Immunol] Abstract

The Retinoic Acid Receptor-Related Orphan Receptor α Positively Regulates Tight Junction Protein Claudin Domain-Containing 1 mRNA Expression in Human Brain Endothelial Cells

Scientists found that claudin domain containing 1 (Cldnd1) and Rora mRNA levels are correlated in rat tissues and that RORα overexpression in human brain endothelial cells enhanced CLDND1 transcript expression. [J Biochem] Abstract

Dysregulation of Vascular Endothelial Growth Factor Receptor-2 by Multiple miRNAs in Endothelial Colony-Forming Cells of Coronary Artery Disease

To identify the miRNA-vascular endothelial growth factor receptor-2 (VEGFR2)-dependent regulation of endothelial colony-forming cells (ECFC) functions, researchers isolated ECFCs from peripheral blood of disease-free and coronary artery disease individuals were subjected to small RNA sequencing for identification of anti-VEGFR2 miRNAs. They determined the angiogenic activities of the miRNAs in both in vitro and in vivo mice models. [J Vasc Res] Abstract

Neutrophil-Mediated Vascular Barrier Injury: Role of Neutrophil Extracellular Traps

The authors highlight recent research findings about neutrophil-mediated signaling and structural changes, including those induced by neutrophil extracellular traps, which ultimately lead to vascular barrier injury. [Microcirculation] Abstract

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Positive Topline Results of Large Phase III Trial Show Eisai’s Lenvatinib Meets Primary Endpoint in Unresectable Hepatocellular Carcinoma

Eisai Inc. announced positive topline results from the randomized, multicenter Phase III trial evaluating the company’s multiple receptor tyrosine kinase inhibitor, lenvatinib, for the first-line treatment of patients with unresectable hepatocellular carcinoma. The trial achieved its primary endpoint by meeting the statistical criteria for non-inferiority of overall survival with lenvatinib compared to sorafenib, the current standard of care for systemic treatment in this setting. [Eisai Inc. (PR Newswire Association LLC.)] Press Release

Seattle Biotech Neovia Begins Clinical Trial for Immunotherapy Enhancing Cancer Drug

Seattle biotech Neovia Oncology has enrolled its first patient into a Phase I clinical trial for its lead cancer drug NEV-801, a novel, multi-inhibitor drug able to enhance immunotherapy response in patients with advanced drug-resistant cancers. [Neovia Oncology Ltd.] Press Release

Proposed U.S. Biotech Rules Raise Industry Hopes and Anxieties

Makers of genetically engineered products have long been on the lookout for changes in U.S. regulations. The system that divvies up the safety review of these products between the Food and Drug Administration, Environmental Protection Agency, and U.S. Department of Agriculture is in the middle of a years-long overhaul, in part to accommodate modern gene-editing technologies such as CRISPR. And a set of new proposals released last week offers hints about what those agencies still hope to change. [ScienceInsider] Editorial

Trump Agenda Threatens US Legacy of Science Diplomacy

A newly minted leader with no experience governing at home or establishing policy abroad now oversees the United States’ vast diplomatic enterprise. US President Donald Trump has a deep bench of scientific and technical expertise to tap across multiple government agencies — but it is not clear that he will use it. [Nature News] Editorial

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

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NEW Postdoctoral Fellow – Glycobiology (Radboud University Nijmegen Medical Centre)

NEW Postdoctoral Fellow – Cardiovascular Developmental Biology (KU Leuven)

Postdoctoral Research Scientist – Small Molecule-Driven Stem and Stem-Like Cell Reprogramming (University of Oxford)

Assistant/Associate Professor – Angiogenesis in Urology (Northwestern University)

PhD Position – Genome Engineering (KU Leuven, Stem Cell Institute)

Postdoctoral Fellow – Cardiovascular Research (Thomas Jefferson University)

Postdoctoral Fellow – Vascular Control of Immune Cell Infiltration and Metastasis (German Cancer Research Center)

Postdoctoral Fellow – Tumor Angiogenesis (Thomas Jefferson University)

Postdoctoral Associate – Molecular Biology (Virginia Commonwealth University)

Postdoctoral Fellow – Endothelial Cell Dysfunction and GPCR Signaling in Vascular Diseases (The University of Tennessee Health Science Center)

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