Endothelial Cell News Volume 2.15 | May 1 2017

TOP STORY

Tumor Ischemia by Interferon-γ Resembles Physiological Blood Vessel Regression

Researchers used a model of interferon-γ (IFNγ) induction and an IFNγ–GFP fusion protein in large, vascularized tumors growing in mice that expressed the IFNγ receptor exclusively in defined cell types. Responsiveness to IFNγ by myeloid cells and other hematopoietic cells, including T cells or fibroblasts, was not sufficient for IFNγ-induced tumor regression, whereas responsiveness of endothelial cells to IFNγ was necessary and sufficient. [Nature] Abstract

(Ranked by impact factor of the journal)

Mural Lymphatic Endothelial Cells Regulate Meningeal Angiogenesis in the Zebrafish

Using transgenic zebrafish, the authors identified a population of isolated mural lymphatic endothelial cells surrounding meningeal blood vessels. These meningeal mural lymphatic endothelial cells expressed lymphatic endothelial cell markers and formed by sprouting from blood vessels. [Nat Neurosci] Abstract

Neurons Secrete miR–132-Containing Exosomes to Regulate Brain Vascular Integrity

Using intact zebrafish larvae and cultured rodent brain cells, investigators found that neurons transfer miR–132, a highly conserved and neuron-enriched microRNA, via secreting exosomes to endothelial cells (ECs) to maintain brain vascular integrity. Following translocation to ECs through exosome internalization, miR–132 regulated the expression of vascular endothelial cadherin, an important adherens junction protein, by directly targeting eukaryotic elongation factor 2 kinase. [Cell Res] Full Article

Hypoxic Lung Cancer-Secreted Exosomal miR-23a Increased Angiogenesis and Vascular Permeability by Targeting Prolyl Hydroxylase and Tight Junction Protein ZO-1

Scientists aimed to clarify how hypoxia affects tumor angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2, leading to the accumulation of hypoxia-inducible factor-1 α in endothelial cells. [Oncogene] Abstract

Insulin Resistance in Vascular Endothelial Cells Promotes Intestinal Tumor Formation

Because hyperinsulinemia is an independent risk factor for cancer development, investigators examined tissue-specific insulin action in intestinal tumor formation. In vitro, insulin increased proliferation of intestinal tumor epithelial cells by almost two-fold in primary culture of tumor cells from Apc^Min/+ mice. They generated Apc^Min/+ mice with loss of insulin receptors in vascular endothelial cells. [Oncogene] Abstract

Tumor Vascular Leakage Defect Due to Endothelium-Targeted FAK-Kinase Dead Mutation Is Abrogated by FAK-Y397E Expression

Researchers developed three Pdgfb-iCre^ert-driven endothelial-cell (EC)-specific, tamoxifen-inducible homozygous mutant mouse lines: FAK wild-type (WT), FAK kinase-dead (KD), and double mutant (DM); KD with a putatively phosphomimetic Y397E mutation. These ECCre+;FAK^WT/WT, ECCre+;FAK^KD/KD and ECCre+;FAK^DM/DM mice were injected subcutaneously with syngeneic B16F0 melanoma cells. Tumor growth and vessel density were decreased in ECCre+;FAK^KD/KD and ECCre+;FAK^DM/DM mice, compared to Cre^– littermates. [J Pathol] Abstract

Ehmt2/G9a Controls Placental Vascular Maturation by Activating the Notch Pathway

The authors showed that the histone methyltransferase Ehmt2, also known as G9a, activates the Notch pathway to promote placental vascular maturation. Placental vasculature from embryos with G9a-deficient endothelial progenitor cells failed to expand due to decreased endothelial cell proliferation and increased trophoblast proliferation. [Development] Abstract | Full Article

Hedgehog Signaling Pathway Orchestrates Angiogenesis in Triple-Negative Breast Cancers

Expression and regulation of the Hedgehog pathway transcription factor glioma-associated oncogene homolog1 protein were studied on the endothelial compartment and on triple-negative breast cancer (TNBC)-initiated angiogenesis. In TNBC xenografted mice, scheduling NVP-LDE225 rather than bevacizumab provided a better sustained inhibition of TNBC cells proliferation and endothelial cells organization. [Br J Cancer] Full Article

Double-Stranded DNA Induces a Prothrombotic Phenotype in the Vascular Endothelium

While effects of double-stranded DNA (dsDNA) in immune cells have been extensively studied, dsDNA signaling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. Scientists aimed to characterize prothrombotic effects of dsDNA in vascular endothelial cells. [Sci Rep] Full Article

Fusions of Tumor-Derived Endothelial Cells with Dendritic Cells Induces Antitumor Immunity

Researchers aimed to explore whether dendritic cells/tumor-derived endothelial cells (DC/EC) fusion cells are potent stimulators of T cells, impacting tumor progression. In vivo, T cells stimulated by DC/EC fusion cells effectively repressed tumor growth. [Sci Rep] Full Article

Pinocembrin Ex Vivo Preconditioning Improves the Therapeutic Efficacy of Endothelial Progenitor Cells in Monocrotaline-Induced Pulmonary Hypertension in Rats

Scientists investigated the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. [Biochem Pharmacol] Abstract | Graphical Abstract

Mitochondria in Endothelial Cells: Sensors and Integrators of Environmental Cues

Endothelial cells are central elements in vessel homeostasis and regulate the passage of material and cells into and out of the bloodstream. The authors discuss the physiological actions of these signals and aberrant responses during vascular disorders. [Redox Biol] Full Article

Context-Dependent Function of ROS in the Vascular Endothelium: The Role of the Notch Pathway and Shear Stress

Scientists describe the way reactive oxygen species (ROS) interact with the Notch pathway and shear stress protecting from — or promoting — the development of endothelial dysfunction. [Biofactors] Abstract

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

Michael A Gimbrone, Jr, M.D., to Receive the ASIP 2017 Gold-Headed Cane Award

The 2017 recipient of the Gold-Headed Cane Award is Dr. Michael A Gimbrone, Jr, Director of the Center for Excellence in Vascular Biology at Brigham and Women’s Hospital and the Elsie T Friedman Professor of Pathology at Harvard Medical School. He discovered methods to isolate and culture endothelial cells from human umbilical vein. [Harvard Medical School (EurekAlert!)] Press Release

Bayer Receives FDA Approval for Stivarga^® (Regorafenib) for the Second-Line Systemic Treatment of Liver Cancer

Bayer announced that the U.S. Food and Drug Administration (FDA) approved Stivarga^® tablets for the second-line treatment of patients with hepatocellular carcinoma who have been previously treated with Nexavar^®. [Bayer AG] Press Release

How Science Fares in the U.S. Budget Deal

Congress has finally reached a deal on spending bills for the 2017 fiscal year. House of Representatives and Senate leaders announced that they expect lawmakers to vote on an agreement that wraps together all 12 appropriations bills that fund federal operations. For the past seven months, the government has been operating under a continuing resolution that froze 2017 spending at most agencies at 2016 levels and generally prevented them from starting new programs. [ScienceInsider] Editorial

Controversial UK Research Reform Crosses Finish Line

A controversial and wide-ranging shake-up of the United Kingdom (UK)’s research and higher-education landscape has been completed, amid a huge rush by the country’s parliament to push through legislation. [Nature News] Editorial

$10 Million Settlement over Alleged Misconduct in Boston Heart Stem Cell Lab

A research misconduct investigation of a prominent stem cell lab by the Harvard University-affiliated Brigham and Women’s Hospital in Boston has led to a massive settlement with the U.S. government over allegations of fraudulently obtained federal grants. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Biomaterials & Tissue Engineering
July 23-28, 2017
Holderness, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Cardiopulmonary Molecular Biology (Hannover Medical School)

NEW Research Scientist – Corneal Endothelial Cells (The Veneto Eye Bank Foundation)

NEW PhD Fellow – Ophthalmology (KU Leuven)

NEW Postdoctoral Fellow – Blood Pressure Regulation (University of Tennessee Health Science Center)

Postdoctoral Fellow – Vascular Biology (University Hamburg-Eppendorf)

Postdoctoral Research – Endothelial Biology (University of South Florida)

Postdoctoral Position – Intersectional Genetics (VIB)

Research Assistant Professor – Endothelial and Epithelial Barrier Function (University of Chicago)

Postdoctoral Follow – Endothelial Cell Ion Channels (The University of Tennessee Health Science Center)

PhD Student – Brain Vascular Biology (ETH Zurich)

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