Endothelial Cell News Volume 3.38 | Nov 19 2018

TOP STORY

Apolipoprotein E Peptide-Directed Chimeric Polymersomes Mediate an Ultrahigh-Efficiency Targeted Protein Therapy for Glioblastoma

Scientists report that apolipoprotein E peptide specifically bound to low-density lipoprotein receptor members and mediated superb blood-brain barrier crossing and highly efficient glioblastoma-targeted protein therapy in vivo. [ACS Nano] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Bi-Directional Signaling by Membrane-Bound KitL Induces Proliferation and Coordinates Thymic Endothelial Cell and Thymocyte Expansion

Activation of membrane-associated KitL (KitL) in thymic vascular endothelial cells (VECs) induced mKitL- and Akt-dependent proliferation, and genetic ablation of mKitL in thymic VECs blocked their c-Kit responsiveness and proliferation during neonatal thymic expansion. Therefore, mKitL–c-Kit formed a bi-directional signaling complex that acted in the developing thymus to coordinate thymic VEC and early thymic progenitor (ETP) expansion by simultaneously promoting ETP survival and VEC proliferation. [Nat Commun] Full Article

Endothelial Cell Rearrangements during Vascular Patterning Require PI3-Kinase-Mediated Inhibition of Actomyosin Contractility

Researchers showed that PI3Kα regulated endothelial cell rearrangements using a combination of a PI3Kα-selective inhibitor and endothelial-specific genetic deletion to abrogate PI3Kα activity during vessel development. [Nat Commun] Full Article

Genetic Variant at Coronary Artery Disease and Ischemic Stroke Locus 1p32.2 Regulates Endothelial Responses to Hemodynamics

Using statistical analyses, assay of transposase accessible chromatin with whole-genome sequencing, H3K27ac/H3K4me2 ChIP with whole-genome sequencing, and CRISPR interference in human aortic endothelial cells, scientists demonstrated that rs17114036, a common noncoding polymorphism at 1p32.2, was located in an endothelial enhancer dynamically regulated by hemodynamics. [Proc Natl Acad Sci USA] Full Article | Press Release

EGFL6 Promotes Breast Cancer by Simultaneously Enhancing Cancer Cell Metastasis and Stimulating Tumor Angiogenesis

Researchers found that EGFL6 reduced apoptotic signaling in cancer cells and promoted tumor growth in vivo. Importantly, expression of EGFL6 in cancer cells and tumor endothelial cells not only increased tumor angiogenesis but also promoted migration of cancer cells. [Oncogene] Full Article

Patient-Specific iPSC-Derived Endothelial Cells Provide Long-Term Phenotypic Correction of Hemophilia A

Investigators generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34⁺ cells and differentiated them into functional endothelial cells secreting factor VIII for gene and cell therapy approaches to cure hemophilia A, an X-linked bleeding disorder caused by F8 mutations. [Stem Cell Reports] Full Article | Graphical Abstract

Inhibition of Kir2.1 Channel-Induced Depolarization Promotes Cell Biological Activity and Differentiation by Modulating Autophagy in Late Endothelial Progenitor Cells

Treatment with the inward rectifier potassium channel 2.1 (Kir2.1)-selective inhibitor ML133 or knockdown of Kir2.1 by shRNA triggered endothelial progenitor cell (EPC) depolarization and promoted EPC biological functions, such as migration, adhesion, angiogenesis and differentiation into endothelial cells in vitro. [J Mol Cell Cardiol] Abstract

Autophagy Promotes Angiogenesis via AMPK/Akt/mTOR Signaling during the Recovery of Heat-Denatured Endothelial Cells

Scientists investigated the relation of autophagy and angiogenesis during the recovery of heat-denatured endothelial cells. A rat deep partial-thickness burn model and a heat-denatured HUVEC model were used. [Cell Death Dis] Full Article

Identification of DKK-1 as a Novel Mediator of Statin Effects in Human Endothelial Cells

Investigators found that atorvastatin downregulated DKK-1 protein and mRNA expression through the inhibition of Cdc42, Rho and Rac geranylgeranylated proteins. Further, a combined approach based on the integration of label-free quantitative mass spectrometry based-proteomics and gene silencing allowed them to demonstrate that DKK-1 itself mediated, at least in part, statin effects on human endothelial cells. [Sci Rep] Full Article

The TRPC5 Channel Regulates Angiogenesis and Promotes Recovery from Ischemic Injury in Mice

Researchers demonstrated that transient receptor potential canonical 5 (TRPC5) was involved in endothelial cell sprouting, angiogenesis and blood perfusion in an oxygen-induced retinopathy model and a hind-limb ischemia model. [J Biol Chem] Abstract | Full Article

Platelet Microparticles Contribute to Aortic Vascular Endothelial Injury in Diabetes via the mTORC1 Pathway

Platelet microparticles (PMPs) inhibited endothelial nitric oxide levels to about 50% and caused approximately twofold increase in reactive oxygen species production. Furthermore, PMPs significantly decreased the endothelial glycocalyx area and expression levels of glypican-1 and occludin. The PMP-induced endothelial injuries were prevented by raptor siRNA and rapamycin. [Acta Pharmacologica Sinica] Full Article

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Distinct Role of Autophagy on Angiogenesis: Highlights on the Effect of Autophagy in Endothelial Lineage and Progenitor Cells

The authors highlight the fundamental role of cell autophagic response in endothelial cells function, stem cells dynamic, and differentiation rate. It seems that elucidation of the mechanisms related to pro- and/or anti-angiogenic potential of autophagy inside endothelial cells and stem cells could help us to modulate stem cell therapeutic features post-transplantation. [Stem Cell Res Ther] Full Article

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European Commission Approves Ipsen’s Cabometyx^® (Cabozantinib) for the Treatment of Hepatocellular Carcinoma in Adults Previously Treated with Sorafenib

Ipsen announced that the European Commission has approved Cabometyx^® 20, 40, 60 mg as a monotherapy for hepatocellular carcinoma in adults who have previously been treated with sorafenib. [Ipsen] Press Release

AVEO Oncology Announces Phase III TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma Meets Primary Endpoint

AVEO Oncology announced positive topline results from the primary analysis of the TIVO-3 trial, the company’s Phase III randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA^®) to sorafenib in 351 subjects with highly refractory advanced or metastatic renal cell carcinoma. [AVEO Oncology] Press Release

Ophthotech Announces Results from Phase IIa Safety Trial of Zimura^® in Combination with Lucentis^® in Wet Age-Related Macular Degeneration

Ophthotech Corporation announced the results from its Phase IIa safety trial of Zimura^®, the company’s complement factor C5 inhibitor, in patients with wet age-related macular degeneration. [Ophthotech Corporation] Press Release

IU Philanthropic Venture Fund Invests in Regenerative Medicine Company Vascugen

The Indiana University (IU) Philanthropic Venture Fund has invested in Vascugen Inc., a regenerative medicine company. Vascugen Inc. is focused on finding therapies to repair human tissue damaged by reduced blood flow due to disease or injury. [Vascugen Inc.] Press Release

Duke University to Settle Case Alleging Researchers Used Fraudulent Data to Win Millions in Grants

Duke University in Durham, North Carolina, is on the verge of settling a case brought by a former employee who claims the university included faked data in applications and reports for federal grants worth nearly $200 million. [ScienceInsider] Editorial

French Science Behemoth Launches Research-Integrity Office

France’s national research center, the CNRS, has announced plans to create its first office of research integrity to investigate scientific misconduct and promote good research practice. [Nature News] Editorial

In Reversal, NSF Lifts Proposal Limits on Biologists

In a reversal, the National Science Foundation (NSF) will no longer restrict researchers to only one proposal submission per year to the biology directorate’s three core tracks in which they are listed as a principal investigator (PI) or co-PI. [ScienceInsider] Editorial

NEW Gordon Research Conference: Vascular Cell Biology
January 20-25, 2019
Ventura, California, United States

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

NEW Senior Research Assistant – Genitourinary Medical Oncology (MD Anderson Cancer Center)

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

NEW Postdoctoral Positions – Angiogenesis and Vascular Metabolism (VIB)

NEW Postdoctoral Research Associate – Endothelial Cell Research (University of Illinois)

Postdoctoral Positions – Cell/Developmental/Vascular Biology (Uppsala University)

Postdoctoral Fellow – Endothelial Cell Research (University of Missouri)

Postdoctoral Position – Molecular/Cell Biology of Neurodegeneration and Alzheimer’s Disease (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Vascular Research (Johns Hopkins University School of Medicine)

Postdoctoral Fellow – Vascular Development (University of Colorado Denver)

Group Leader – Vascular Research (Helmholtz Zentrum München)

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