Endothelial Cell News Volume 4.05 | Feb 11 2019

TOP STORY

MicroRNA-Dependent Regulation of Biomechanical Genes Establishes Tissue Stiffness Homeostasis

Inhibition of DROSHA or argonaute 2, or disruption of microRNA recognition elements within individual target mRNAs, such as connective tissue growth factor, induced hyper-adhesive, hyper-contractile phenotypes in endothelial and fibroblast cells in vitro, and increased tissue stiffness, contractility and extracellular matrix deposition in the zebrafish fin fold in vivo. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Mature Vessel Networks in Engineered Tissue Promote Graft-Host Anastomosis and Prevent Graft Thrombosis

Monitoring graft-host interactions postimplantation demonstrated that the 14-day in vitro-cultured grafts, bearing more mature and complex vessel networks as indicated by elongated and branched vessel structures, had increased graft-host vessel anastomosis; host vessel penetration into the graft increased approximately eightfold, and graft perfusion increased sixfold. [Proc Natl Acad Sci USA] Abstract

Increased Gene Copy Number of DEFA1/DEFA3 Worsens Sepsis by Inducing Endothelial Pyroptosis

Human neutrophil peptide 1 (HNP-1) induced endothelial cell pyroptosis via P2X7 receptor-mediating canonical caspase-1 activation in a NLRP3 inflammasome-dependent manner. Based on these findings, the authors engineered a monoclonal antibody against HNP-1 to block the interaction with P2X7 and found that the blocking antibody protected mice carrying high copy number of DEFA1/DEFA3 from lethal sepsis. [Proc Natl Acad Sci USA] Full Article

Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism

Scientists demonstrated that nonstructural protein 1 (NS1) from dengue, Zika, West Nile, Japanese encephalitis, and yellow fever viruses selectively bound to and altered permeability of human endothelial cells from lung, dermis, umbilical vein, brain, and liver in vitro and caused tissue-specific vascular leakage in mice, reflecting the pathophysiology of each flavivirus. [Cell Rep] Full Article | Graphical Abstract

Correlation of Two Distinct Metastasis-Associated Proteins, MTA1 and S100A4, in Angiogenesis for Promoting Tumor Growth

Non-muscle myosin IIA phosphorylation, which was partly controlled by S100A4, was found to be upregulated by knockdown of both proteins in MSS31 cells. Moreover, cycloheximide treatment of MSS31 cells revealed that the rate of S100A4 degradation was accelerated by MTA1 knockdown. [Oncogene] Abstract

Hypoxic Cancer-Associated Fibroblasts Increase NCBP2-AS2/HIAR to Promote Endothelial Sprouting through Enhanced VEGF Signaling

Investigators found that hypoxic human mammary cancer-associated fibroblasts (CAFs) promoted angiogenesis in CAF-endothelial cell cocultures in vitro. Mass spectrometry-based proteomic analysis of the CAF secretome unraveled that hypoxic CAFs contributed to blood vessel abnormalities by altering their secretion of various pro- and anti-angiogenic factors. [Sci Signal] Abstract

Extracellular Vesicles from Kaposi Sarcoma-Associated Herpesvirus Lymphoma Induce Long-Term Endothelial Cell Reprogramming

Extracellular vesicle contents can be modified by the cell in response to stimuli, allowing them to relay information to neighboring cells, influencing their physiology. Here, researchers showed that the tumor virus Kaposi’s Sarcoma-associated herpesvirus hijacked this signaling pathway to induce cell proliferation, migration, and transcriptome reprogramming in cells not infected with the virus. [PLoS Pathog] Full Article

Ser46 Phosphorylation of p53 Is an Essential Event in Prolyl-Isomerase Pin1-Mediated p53-Independent Apoptosis in Response to Heat Stress

Heat stress (HS) caused an increase in p53 phosphorylation at Ser46 that facilitated interactions with phosphorylation-dependent prolyl-isomerase Pin1, which had a key role in promoting HS-induced localization of p53 to mitochondria. [Cell Death Dis] Full Article

Functional Equivalency in Human Somatic Cell Nuclear Transfer – Derived Endothelial Cells

The isolated CD31⁺ cells exhibited hallmark endothelial characteristics in terms of morphology, tubule formation, and ac-LDL uptake. Furthermore, CHA-NT4 derived endothelial cell transplantation in hindlimb ischemic mice rescued the hindlimb and restored blood perfusion. [Stem Cells] Abstract

Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation

Transient receptor potential vanilloid-2 (TRPV2) expression and its role on Ca²⁺ cellular dynamics, trans-endothelial electrical resistance, cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of human brain microvessel endothelial cells or in the human cerebral microvessel endothelial hCMEC/D3 cell line. [Molecular Pharmaceutics] Abstract | Graphical Abstract

Activator of G-Protein Signaling 8 Is Involved in VEGF-Induced Choroidal Neovascularization

Activator of G-protein signaling 8 (AGS8) knockdown in cultured choroidal endothelial cells inhibited VEGF-induced VEGFR-2 phosphorylation, cell proliferation, and migration. AGS8 knockdown also downregulated cell sprouting from mouse choroidal tissue in ex vivo culture. [Sci Rep] Full Article

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The Role of Osteoprotegerin and Its Ligands in Vascular Function

The authors review the role of the osteoprotegerin/receptor activators of nuclear factor kappa-B (RANK) ligand/RANK triad in vascular function as well as molecular mechanisms related to the etiology of vascular diseases. The potential therapeutic strategies may be very promising in the future. [Int J Mol Sci] Full Article

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One-Year Results from Positive Phase III EYLEA Trial in Diabetic Retinopathy Presented

Regeneron Pharmaceuticals, Inc. announced that positive detailed one-year results from the Phase III PANORAMA trial evaluating EYLEA^® injection in patients with moderately severe to severe non-proliferative diabetic retinopathy were presented. [Press release from Regeneron Pharmaceuticals, Inc. discussing research presented at the Angiogenesis, Exudation, and Degeneration 2019 symposium, Miami] Press Release

Avalon GloboCare Announces Breakthrough in Identifying Human Angiogenic Exosomes/Extracellular Vesicles (EV) Derived from Endothelial Cells

Avalon GloboCare Corp. announced that its ongoing co-development program with Weill Cornell Medicine, led by Yen-Michael Hsu, MD, PhD, Director of cGMP Cellular Therapy Facility and Laboratory for Advanced Cellular Engineering, has identified novel human angiogenic exosomes/EV derived from endothelial cells. [Avalon GloboCare Corp.] Press Release

Temple’s Dr. Arthur Feldman Recognized with American College of Cardiology Top Honor

The Distinguished Scientist Award-Basic Domain is awarded to a Fellow of the American College of Cardiology who has made major scientific contributions to the advancement of scientific knowledge in the field of cardiovascular disease. [Temple University Health System, Inc.] Press Release

France Set to Get First National Strategy for Research

France is preparing to implement a national, multi-year research plan for the first time – a move warmly welcomed by the heads of the country’s major research agencies. [Nature News] Editorial

Ukraine’s Science Revolution Stumbles Five Years On

Ukraine’s science system is in a precarious state, despite promised improvements in the wake of a revolution five years ago that aligned the country with the European Union. [Nature News] Editorial

NEW Gordon Research Seminar: New Views of Organogenesis and Tumorigenesis: From Single Molecules to Therapeutics
March 23-24, 2019
Ventura, California, United States

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NEW Tier 2 Canada Research Chair – Cardiovascular/Vascular Health (University of Ottawa)

Faculty Position – Clinical & Experimental Therapeutics (Augusta University)

Postdoctoral Position – Cardiovascular Research (University of Hawaii)

Postdoctoral Research Assistant – Endothelial Heterogeneity (University of Oxford)

Postdoctoral Fellows – Vascular Immunology & Immunotherapy (Uppsala University)

Assistant Professor – Sarcoma & Skeletal-Related Malignancies (UC Davis School of Medicine)

Assistant Professor Tenure Track – Epithelial Cell Biology (Boston Children’s Hospital)

Postdoctoral Fellowship – Vascular & Valvular Biology (Yale University School of Medicine)

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

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

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