Endothelial Cell News Volume 4.10 | Mar 25 2019

TOP STORY

Endothelial SIRT6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury through Targeting Nkx3.2-GATA5 Signaling

Functionally, SIRT6 had pleiotropic protective actions in endothelial cells which included promoting endothelium-dependent vasodilatation and vascular nitric oxide bioavailability, reducing cellular permeability, ameliorating endothelial senescence and apoptosis, and facilitating autophagy. Mechanistically, SIRT6 induced the expression of GATA5, a novel regulator of blood pressure, through inhibiting Nkx3.2 transcription by deacetylating histone H3K9, thereby regulating GATA5-mediated signaling pathways to prevent endothelial injury. [Circ Res] Abstract

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piRNA-823 Delivered by Multiple Myeloma-Derived Extracellular Vesicles Promoted Tumorigenesis through Re-Educating Endothelial Cells in the Tumor Environment

Increased piwi-interacting RNA (piRNA)-823 expression was associated with late stages and poor prognosis of multiple myeloma (MM). The MM-derived-extracellular vesicles effectively transferred piRNA-823 to EA.hy926 endothelial cells. The piRNA-823 mimic and inhibitor were designed to upregulate or to suppress the endogenous function of piRNA-823. [Oncogene] Abstract

Mineralocorticoid Receptor Negatively Regulates Angiogenesis through Repression of STAT3 Activity in Endothelial Cells

Mineralocorticoid receptor (MR) knockout (MRKO) and MR knockdown both upregulated gene expression, protein level, and phosphorylation of signal transducer and activator of transcription 3 (STAT3). Stattic, a selective STAT3 inhibitor, attenuated the effects of MRKO on tube formation, migration and proliferation of endothelial cells. [J Pathol] Abstract

MicroRNA-145 Regulates Pathological Retinal Angiogenesis by Suppression of TMOD3

In cultured human retinal endothelial cells (ECs), treatment with miR-145 mimics significantly increased EC angiogenic function including proliferation, migration, and tubular formation; whereas miR-145 inhibitors attenuated in vitro angiogenesis. Tropomodulin3 (TMOD3), an actin-capping protein, was a direct miR-145 target, and was downregulated in oxygen-induced retinopathy retinas. Treatment with miR-145 mimic led to TMOD3 inhibition, altered actin cytoskeletal architecture, and EC cell shape elongation. [Mol Ther Nucleic Acids] Abstract | Full Article

Recombinant RGD-Disintegrin DisBa-01 Blocks Integrin α_vβ₃ and Impairs VEGF Signaling in Endothelial Cells

DisBa-01 treatment of endothelial cells inhibited critical steps of VEGF-mediated angiogenesis such as migration, invasion and tubulogenesis. The blockage of α_vβ₃ /VEGF type 2 receptor (VEGFR2) cross-talk by this disintegrin decreased protein expression and phosphorylation of VEGFR2 and β₃ integrin subunit, regulated FAK/SrC/Paxillin downstream signals, and inhibited ERK1/2 and PI3K pathways. [Cell Commun Signal] Full Article

Egr1 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus via Promoting p53 Transcription

Down-regulation of early growth response 1 (Egr1) in human retinal vascular endothelial cells under high-glucose conditions inhibited apoptosis, migration and tube formation in vitro. Moreover, sh-Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function by decreasing apoptotic cells and microvascular formation in vivo. [J Cell Mol Med] Full Article

Andrographolide Attenuates Imbalance of Gastric Vascular Homeostasis Induced by Ethanol through Glycolysis Pathway

Andrographolide treatment inhibited HUVEC-C activity characterized by suppressing proliferation and migration of endothelial cells. Mechanically, andrographolide treatment significantly suppressed the expression of glycolytic genes, especially decreasing PFKFB3 expression. [Sci Rep] Full Article

Putative Endothelial Progenitor Cells Do Not Promote Vascular Repair but Attenuate Pericyte-Myofibroblast Transition in UUO-Induced Renal Fibrosis

In vitro, putative endothelial progenitor cells were co-cultured with renal-derived pericytes. Pericyte-myofibroblast transition was evaluated using the myofibroblast marker α-smooth muscle actin and pericyte marker platelet-derived growth factor receptor β. [Stem Cell Res Ther] Full Article

An Interaction between BRG1 and Histone Modifying Enzymes Mediates Lipopolysaccharide-Induced Proinflammatory Cytokines in Vascular Endothelial Cells

The researchers investigated the interplay between different epigenetic factors during lipopolysaccharide induced synthesis of proinflammatory cytokines in cultured vascular endothelial cells. [J Cell Biochem] Abstract

Cholesterol Modification of SDF-1-Specific siRNA Enables Therapeutic Targeting of Angiogenesis through Akt Pathway Inhibition

Rat endothelial progenitor cells and bone marrow mesenchymal stem cells (BMSCs) showed high stromal cell-derived factor 1 (SDF-1) mRNA expression, which could be down-regulated by using chol-siSDF-1. Chol-siSDF-1 could significantly inhibit the migration of BMSCs and HUVECs. [Exp Eye Res] Abstract

Inhibition of VEGFR-2 Phosphorylation and Effects on Downstream Signaling Pathways in Cultivated Human Edothelial Cells by Stilbenes from Vitis spp

VEGF receptor 2 (VEGFR-2) activation was studied through an ELISA assay in a HUVEC line while the phosphorylation of intracellular downstream proteins PLCγ1, Akt and eNOS were tested by western-blot. Student’s t-test was used to determine significant differences between samples. Astringin, pallidol and ω-viniferin showed the lowest IC50 values against VEGFR-2 activation. [J Agric Food Chem] Abstract

Clinically Relevant Concentrations of Lidocaine Inhibit Tumor Angiogenesis through Suppressing VEGF/VEGFR2 Signaling

Lidocaine at clinically relevant concentrations inhibited angiogenesis. Lidocaine inhibited endothelial cell in vitro capillary network formation on Matrigel through interfering at an early stage of angiogenesis. In addition, lidocaine inhibited vascular endothelial growth factor-stimulated endothelial cell migration and proliferation without affecting cell adhesion. [Cancer Chemother Pharmacol] Abstract

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Two Birds, One Stone: Double Hits on Tumor Growth and Lymphangiogenesis by Targeting Vascular Endothelial Growth Factor Receptor 3

The authors discuss current findings related to VEGF-C/VEGF receptor 3 (VEGFR3) signaling in cancer progression and recent advances in the development of therapeutic drugs targeting VEGF-C/VEGFR3. [Cells] Full Article

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Alkahest Presents Positive Results from Phase IIa Open Label Study of AKST4290

The study evaluated the therapeutic effect and safety of the small molecule, AKST4290, formerly known as ALK4290, for the treatment of wet or neovascular age-related macular degeneration in treatment-naïve patients. [Press release from Alkahest, Inc. (PR Newswire Association LLC.) discussing research presented at the 2019 Retina World Congress, Fort Lauderdale] Press Release

Historic Partnership between the Weizmann Institute of Science and Institut Curie

The Weizmann Institute of Science in Rehovot, Israel, and Institut Curie in Paris, France, signed an historic partnership that will allow their teams to work closely together to improve knowledge in the field of life sciences, particularly in the areas of physics and chemistry, and most specifically – in the field of cancer research. [Weizmann Institute of Science] Press Release

Scientists Among Thousands Marching to Demand Say on Brexit

Scientists took to the streets of London on 23 March as part of a major demonstration calling for the terms of Brexit to be put to the British people in a vote. [Nature News] Editorial

Chinese-American Scientist Societies Fear Racial Profiling

In a strongly worded letter published in Science, a group of Chinese-American scientists voiced concern that recent proposals from the National Institutes of Health and FBI actions could lead to unjust targeting of ethnically Chinese scientists. [The Scientist] Editorial

Universities Spooked by Trump Order Tying Free Speech to Grants

US President Donald Trump is expected to issue an executive order on 21 March that would require universities to certify that they protect free speech or risk losing federal research funds. The order will apply to 12 research agencies, including the National Institutes of Health, the National Science Foundation, the Department of Energy and NASA, a White House official said. [Nature News] Editorial

NEW Keystone Symposia: Delivering Therapeutics Across Biological Barriers
May 6-9, 2019
Dublin, Ireland

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NEW PhD Position – Vascular Biology (Uppsala University)

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

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

Postdoctoral Research Assistant – Cancer & Vascular Biology (University of Oxford)

Faculty Position – Bioengineering (University of Pittsburgh)

Postdoctoral Position – Endothelial Cell Protection (University of Bern)

Vascular Biologist – RNA Therapeutics (Guide Therapeutics)

Postdoctoral Fellow – Vascular Biology (Stanford School of Medicine)

Postdoctoral Fellow – Vascular Biology (University of Nevada, Reno)

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)

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

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