Endothelial Cell News Volume 4.13 | Apr 15 2019

TOP STORY

Deubiquitinase USP10 Regulates Notch Signaling in the Endothelium

Scientists found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in endothelial cells. [Science] Abstract

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The Heparin Binding Domain of von Willebrand Factor Binds to Growth Factors and Promotes Angiogenesis in Wound Healing

Investigators showed that in vitro von Willebrand factor (VWF) bound to several growth factors, including VEGF-A isoforms and platelet derived growth factor-BB, mainly through the heparin-binding domain within the VWF A1 domain. VWF also bound to VEGF-A and FGF-2 in human plasma and co-localized with VEGF-A in endothelial cells. [Blood] Abstract

3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts

The ability to print functional vascularized patches according to a patient’s anatomy was demonstrated. Blood vessel architecture was further improved by mathematical modeling of oxygen transfer. The structure and function of the patches were studied in vitro, and cardiac cell morphology was assessed after transplantation, revealing elongated cardiomyocytes with massive actinin striation. [Adv Sci] Abstract | Editorial

Axitinib Exposure Triggers Endothelial Cells Senescence through ROS Accumulation and ATM Activation

The authors report that axitinib, an inhibitor of VEGF receptors currently in use as a second line treatment for advanced renal cell carcinoma, promoted senescence of human endothelial cells in vitro. A one-hour pulse of axitinib was sufficient for triggering cell senescence. Mechanistically, this required oxidative stress-dependent activation of the ataxia telangiectasia mutated (ATM) kinase. [Oncogene] Abstract

Galloyl Carbohydrates with Antiangiogenic Activity Mediated by Capillary Morphogenesis Gene 2 (CMG2) Protein Binding

In a high-throughput Förster resonant energy transfer-based binding assay, researchers found that one of their synthetic analogues, with mannose as central core and galloyl substituents, exhibited higher affinity for CMG2 than the natural glucose prototype 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose and proved to be a potent angiogenesis inhibitor. [J Med Chem] Abstract | Graphical Abstract

LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) Distinctly Regulate Neutrophil Extravasation through Hotspots I and II

Using two-photon intravital imaging and transmission electron microscopy, scientists observed the existence of preferred sites for neutrophil entrance into the endothelial cell monolayer and exit from the basement membrane and pericyte sheath during neutrophil extravasation, namely, hotspots I and II, by elucidating distinctive roles of LFA-1 and Mac-1. [Exp Mol Med] Full Article

Concomitant Overexpression of Triple Antioxidant Enzymes Selectively Increases Circulating Endothelial Progenitor Cells in Mice with Limb Ischemia

Bone marrow and blood cells were collected for endothelial progenitor cell (EPC) analysis and mononuclear cell intracellular reactive oxygen species production, apoptosis and proliferation at baseline, day 3 and day 21 after ischemia. Cells positive for c-Kit⁺/CD31⁺ or Sca-1⁺/Flk-1⁺ or CD34⁺/CD133⁺ or CD34⁺/Flk-1⁺ were identified as EPCs. [J Cell Mol Med] Full Article

The Pro-Angiogenic Role of Hypoxia Inducible Factor Stabilizer FG-4592 and Its Application in an In Vivo Tissue Engineering Chamber Model

The authors found that FG-4592 promoted tube formation in an in vitro model of angiogenesis by stabilizing hypoxia-inducible factor-1α and activating VEGF. When FG-4592 immobilized fibrin gel scaffold was implanted into a subcutaneous tissue engineering chamber, the vascularization process was significantly enhanced through the similar mechanisms which was verified in vitro. [Sci Rep] Full Article

The Secreted Ly6/uPAR-Related Protein-1 Suppresses Neutrophil Binding, Chemotaxis, and Transmigration through Human Umbilical Vein Endothelial Cells

Secreted Ly-6/uPAR Related Protein-1 (SLURP1) suppressed the primary human neutrophil chemotaxis, and interaction with HUVECs. Furthermore, SLURP1 suppressed formyl Met-Leu-Phe-induced phosphorylation of protein kinase-B in differentiated neutrophil-like HL-60 cells. [Sci Rep] Full Article

Platelet Lysate Inhibits NF-κB Activation and Induces Proliferation and an Alert State in Quiescent Human Umbilical Vein Endothelial Cells Retaining Their Differentiation Capability

Platelet lysate (PL) exerted a protective effect on HUVECs in an inflammatory milieu by inhibiting IL-1α-activated NF-κB pathway and by inducing the secretion of PGE₂, a pro-resolving molecule in the wound microenvironment. Moreover, PL enhanced HUVEC proliferation, without affecting their capability of forming tube-like structures on matrigel, and activated resting quiescent cells to re-enter cell cycle. [Cells] Abstract

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Arterial Lymphatics in Atherosclerosis: Old Questions, New Insights, and Remaining Challenges

The authors provide an overview of factors and mechanisms that regulate lymphangiogenesis, summarize recent findings on the role of lymphatics in macrophage reverse cholesterol transport, immune cell trafficking and pathogenesis of atherosclerosis, and present an overview of pharmacological and genetic strategies to modulate lymphatic vessel density in cardiovascular tissue. [J Clin Med] Abstract

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TRACON Pharmaceuticals Announces Termination of Phase III TAPPAS Trial Based on the Recommendation of the Independent Data Monitoring Committee

TRACON Pharmaceuticals announced that its Phase III TAPPAS trial evaluating TRC105 in combination with Votrient in patients with advanced or metastatic angiosarcoma was terminated for futility based on the recommendation of the Independent Data Monitoring Committee following its review of interim unblinded safety and efficacy data from more than 120 patients enrolled in the trial at the time of the analysis. [TRACON Pharmaceuticals, Inc.] Press Release

Hemostemix Announces Enrollment Milestone in the ACP-01 Phase II Critical Limb Ischemia Clinical Trial

Hemostemix Inc. announced that it has reached an enrollment milestone in its continuing Phase II Clinical Trial for critical limb ischemia (CLI). The company’s patented ACP-01 autologous stem cells have been shown in previous clinical studies to stimulate the generation of new blood vessels in CLI patients and improve amputation-free survival. [Hemostemix Inc.] Press Release

Adverum Biotechnologies Provides Clinical Program Update on ADVM-022 Gene Therapy for Wet AMD

Adverum Biotechnologies, Inc. provided a program update on ADVM-022, a novel, single-administration gene therapy being evaluated in the OPTIC Phase I clinical trial in patients with wet age-related macular degeneration (wet AMD). [Adverum Biotechnologies, Inc.] Press Release

Novartis Announces FDA Filing Acceptance and Priority Review of Brolucizumab (RTH258) for Patients with Wet AMD

Novartis announced that the FDA accepted the company’s Biologics License Application for brolucizumab for the treatment of wet age-related macular degeneration (AMD), also known as neovascular AMD, or nAMD. Seeking to make brolucizumab available as quickly as possible, Novartis used a priority review voucher to expedite FDA review. [Novartis AG] Press Release

Indonesian Mega-Science Agency in the Balance as Election Begins

Indonesians will vote in a national election that pits two old rivals against each other. The stakes are high for science. President Joko Widodo says that if he is re-elected, he will overhaul how much of the country’s research is organized and funded. The main opposition candidate has been silent on science so far. [Nature News] Editorial

African Research Projects Are Failing Because Funding Agencies Can’t Match Donor Money

Although African countries appreciate research grants from donor countries, they often chafe at the condition that they bring in their own money in order to be eligible. Some research projects fall by the wayside because African granting agencies simply have no way to provide their share of the money, sometimes called counterfunding, the heads of 15 national science councils in Africa said at a meeting. [ScienceInsider] Editorial

NEW Advanced Cell Therapies and Tissue Engineering
November 14-16, 2019
Milan, Italy

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NEW Lead Scientist – Cell Phenotyping (Victor Chang Cardiac Research Institute)

NEW Postdoctoral Position – Angiogenesis & Vascular Biology (Johns Hopkins University)

Postdoctoral Scientists – Metabolic Regulation of Vascular Formation (Oklahoma Medical Research Foundation)

Postdoctoral Position – Vascular Tissue Engineering (BioTis)

Postdoctoral Position – Vascular Development (University of Massachusetts Medical School)

Postdoctoral Research Associate – Endothelial Permeability & Vascular Inflammation (University of Illinois at Chicago)

Postdoctoral Research Scientist – Regulatory Pathways During Development (Oxford University)

Postdoctoral Position – Vascular Biology (Albert Einstein College of Medicine)

Faculty Position – Bioengineering (University of Pittsburgh)

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

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