Endothelial Cell News Volume 2.05 | Feb 20 2017

TOP STORY

Cell–Matrix Signals Specify Bone Endothelial Cells during Developmental Osteogenesis

Researchers report that embryonic and early postnatal long bone contained a specialized endothelial cell subtype, termed type E, which strongly supported osteoblast lineage cells and later gave rise to other endothelial cell subpopulations. Loss of endothelial integrin β1 lead to endothelial cell differentiation defects and impaired postnatal bone growth, which was, in part, phenocopied by endothelial cell-specific laminin α5 mutants. [Nat Cell Biol] Abstract

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Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease

Scientists demonstrated in experimental mouse models of diabetic kidney disease (DKD) that renal vascular endothelial growth factor B (VEGF-B) expression correlated with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduced renal lipotoxicity, re-sensitized podocytes to insulin signaling, inhibited the development of DKD-associated pathologies, and prevented renal dysfunction. [Cell Metab] Abstract | Press Release | Graphical Abstract

A Class of Extracellular Vesicles from Breast Cancer Cells Activates VEGF Receptors and Tumor Angiogenesis

The authors describe how a specific class of extracellular vesicles, called microvesicles (MVs), activate VEGF receptors and tumor angiogenesis through a unique 90 kDa form of VEGF (VEGF_90K). They showed that VEGF_90K is generated by the crosslinking of VEGF₁₆₅, catalyzed by the enzyme tissue transglutaminase, and associates with MVs through its interaction with the chaperone Hsp90. [Nat Commun] Full Article

AXL-Dependent Infection of Human Fetal Endothelial Cells Distinguishes Zika Virus from Other Pathogenic Flaviviruses

Investigators showed that when viruses are produced in mammalian cells, Zika virus (ZIKV), but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. They showed that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells, and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. [Proc Natl Acad Sci USA] Full Article | Press Release

Quaking is a Key Regulator of Endothelial Cell Differentiation, Neovascularization and Angiogenesis

Using the model of induced pluripotent stem cell differentiation towards endothelial cells (ECs), researchers found the Quaking isoform 5 (QKI-5) to be an important regulator of STAT3 stabilization and VEGFR2 activation during the EC differentiation process. QKI-5 was induced during EC differentiation, resulting in stabilization of STAT3 expression and modulation of VEGFR2 transcriptional activation as well as VEGF secretion through direct binding to the 3′ UTR of STAT3. [Stem Cells] Full Article

CYP Epoxygenase-Derived H₂O₂ Is Involved in the Endothelium-Derived Hyperpolarization (EDH) and Relaxation of Intrarenal Arteries

The authors sought to investigate whether H₂O₂ is involved in the endothelium-dependent relaxations of intrarenal arteries as well the possible endothelial sources of reactive oxygen species generation involved in these responses. Under conditions of cyclooxygenase and nitric oxide synthase inhibition, acetylcholine induced relaxations and stimulated H₂O₂ release that was reduced by catalase and by the glutathione peroxidase mimetic ebselen in rat renal interlobar arteries, suggesting the involvement of H₂O₂ in the endothelium-dependent responses. [Free Radic Biol Med] Abstract | Graphical Abstract

Suppression of TAK1 Pathway by Shear Stress Counteracts the Inflammatory Endothelial Cell Phenotype Induced by Oxidative Stress and TGF-β1

Investigators hypothesized that shear stress counteracts the inflammatory effects of oxidative stress and TGF-β1 on endothelial cells by restoring redox balance and repressing the TAK1 pathway. Using human umbilical vein endothelial cells, they showed that TGF-β1 aggravates oxidative stress-mediated inflammatory activation and that shear stress activates ERK5 signaling while attenuating TGF-β signaling. [Sci Rep] Full Article

Bone Marrow–Derived MicroRNA-223 Works as an Endocrine Genetic Signal in Vascular Endothelial Cells and Participates in Vascular Injury from Kawasaki Disease

Investigators sought to determine the role of blood microRNA (miR)-223 in Kawasaki disease (KD) and KD-induced injuries in vascular endothelial cells (ECs) as well as the mechanisms involved. In KD patients, the levels of blood cell–derived miR-223 in ECs were significantly increased. [J Am Heart Assoc] Full Article

Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration

Using primary human endothelial progenitor cells (EPCs)/endothelial cells (ECs) as living probes, investigators identified a αvβ3 integrin ligand LXW7 discovered by one-bead-one-compound combinatorial technology as a potent and specific EPC/EC targeting ligand. LXW7 overcame the major barriers of other functional biomolecules that have previously been used to improve vascularization for tissue regeneration, and possessed optimal stability, EPC/EC specificity and functionality. [ACS Chem Biol] Abstract

eIF3i Activity Is Critical for Endothelial Cells in Tumor Induced Angiogenesis through Regulating VEGFR and ERK Translation

Scientists found that a key translational regulator, eIF3i, is highly expressed in endothelial cells during embryonic and tumor angiogenesis. Knockdown of eIF3i restrained cell proliferation and migration in endothelial cells. In a zebrafish angiogenesis model, eIF3i mutant endothelial cells could not respond to induction signals from tumor mass. [Oncotarget] Full Article

The Endothelium Solves Problems That Endothelial Cells Do Not Know Exist

Researchers suggest that the extraordinary sensory capabilities of the endothelium do not come from single cells but from the combined activity of a large number of endothelial cells. Each cell has a limited, but distinctive, sensory capacity and shares information with neighbors so that sensing is distributed among cells. [Trends Pharmacol Sci] Full Article

Lipoprotein(a) and Inflammation: A Dangerous Duet Leading to Endothelial Loss of Integrity

The authors discuss the complex association between inflammation and lipoprotein(a) [Lp(a)]. Findings showing that Lp(a) may promote the expression of a plethora of pro-inflammatory cytokines and induces the endothelium to switch into an activated status which results in adhesion molecules expression and inflammatory cells invasion into the arterial wall. Also, the detrimental duet of inflammation and Lp(a) may interfere with the physiological endothelial repair response, thus further amplifying endothelial loss of integrity and protective functions. [Pharmacol Res] Abstract | Graphical Abstract

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

$9.4 Million Grant Helps Scientists Explore How Cell Death from High Blood Pressure Fuels Even Higher Pressure

Scientists have increasing evidence that when cell carnage increases because of high blood pressure, the mounting debris also gets the attention of our immune system, causing inflammation and blood vessel constriction that contributes to worsening hypertension. Webb, a vascular expert, is principal investigator on a $9.4 million Program Project Grant from the National Heart, Lung and Blood Institute, that will further parse how contents regularly spilt from a surplus of dying cells contribute to this unhealthy and seemingly vicious circle. [Augusta University] Press Release

AVEO Announces Clinical and Regulatory Updates for Tivozanib

AVEO Oncology announced clinical and regulatory updates for its lead drug candidate, tivozanib, an oral, once-daily, vascular endothelial growth factor tyrosine kinase inhibitor. [AVEO Pharmaceuticals, Inc.] Press Release

TRACON Pharmaceuticals Announces Top-Line Results from NCI-Sponsored Phase II Trial of TRC105 in Recurrent Glioblastoma

TRACON Pharmaceuticals reported top-line results from a randomized Phase II clinical trial of TRC105 in recurrent glioblastoma (GBM) funded and conducted by the Clinical Therapy Evaluation Program of the National Cancer Institute (NCI). Top-line data indicate that the combination of TRC105 and Avastin did not improve median progression free survival versus single agent Avastin in recurrent GBM patients, although the combination was associated with a non-significant increase in overall survival. [TRACON Pharmaceuticals, Inc.] Press Release

TRACON Pharmaceuticals Announces First Patient Dosed in Phase III TAPPAS Trial of TRC105 in Angiosarcoma

TRACON Pharmaceuticals announced that it has initiated patient dosing in its Phase III TRC105 and pazopanib versus pazopanib alone in patients with advanced angioSarcoma (TAPPAS) trial of TRC105. [TRACON Pharmaceuticals, Inc.] Press Release

Delay in Hiring Science Advisers Intensifies Brexit Worries

Policy experts want scientists to be at the table when government decides on environmental protection and membership of international collaborations. [Nature News] Editorial

Why the CRISPR Patent Verdict Isn’t the End of the Story

The US Patent and Trademark Office issued a key verdict this week in the battle over the intellectual property rights to the potentially lucrative gene-editing technique CRISPR–Cas9. But the fight for patent rights to CRISPR technology is by no means over. [Nature News] Editorial

NEW Keystone Symposium: Angiogenesis & Vascular Disease
May 8-12, 2017
Santa Fe, United States

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

NEW Postdoctoral Fellow – Stem Cell Biology (Northwestern University)

NEW PhD Position – Blood-Brain Barrier Biology (Technical University of Denmark)

NEW PhD Position – Molecular Biology (Institut of Molecular Biology)

Postdoctoral Fellow – Cardiopulmonary Molecular Biology (Hannover Medical School)

Postdoctoral Fellowship – RNA Biology (Goethe University Frankfurt)

Assistant/Associate Professor – Angiogenesis in Urology (Northwestern University)

PhD Position – Genome Engineering (KU Leuven, Stem Cell Institute)

Postdoctoral Fellow – Cardiovascular Research (Thomas Jefferson University)

Postdoctoral Fellow – Tumor Angiogenesis (Thomas Jefferson University)

Postdoctoral Associate – Molecular Biology (Virginia Commonwealth University)

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