Endothelial Cell News Volume 4.23 | Jul 8 2019

TOP STORY

Exome Sequencing Revealed Notch Ligand JAG1 as a Novel Candidate Gene for Familial Exudative Vitreoretinopathy

Scientists revealed that mutant JAG1 proteins JAG1-A138V and JAG1-T962A lost almost all of their activities, and JAG1-R472H lost approximately 50% of its activity. Deletion of Jag1 in mouse endothelial cells resulted in reduced tip cells at the angiogenic front and retarded vessel growth, reproducing familial exudative vitreoretinopathy-like phenotypes. [Genet Med] Abstract

(Ranked by impact factor of the journal)

Non-Canonical Wnt Signaling Regulates Junctional Mechanocoupling during Angiogenic Collective Cell Migration

Researchers identified that Wnt5a specifically activated Cdc42 at cell junctions downstream of ROR2 to reinforce coupling between adherens junctions and the actin cytoskeleton. They showed that Wnt5a signaling stabilized vinculin binding to alpha-catenin, and abrogation of vinculin in vivo and in vitro led to uncoordinated polarity and deficient sprouting angiogenesis in Mus musculus. [eLife] Abstract

Purinergic P2Y₂ Receptors Modulate Endothelial Sprouting

Overexpression of P2Y₂ in endothelial cells induced the expression of the proangiogenic molecules CXCR4, CD34, and angiopoietin-2, while expression of VEGFR-2 was decreased. Elevated P2Y₂ expression caused constitutive phosphorylation of ERK1/2 and VEGFR-2. However, stimulation of cells with the P2Y₂ agonist UTP did not influence sprouting unless P2Y₂ was constitutively expressed. [Cell Mol Life Sci] Abstract

Canonical Wnt Signaling Promotes Neovascularization through Determination of Endothelial Progenitor Cell Fate via Metabolic Profile Regulation

Isolated endothelial progenitor cells (EPCs) from very low-density lipoprotein receptor knockout mice showed over-activated Wnt signaling, correlating with increased mitochondrial function, mass and DNA copy numbers, compared to WT EPCs. Wnt signaling up-regulated mitochondrial biogenesis and function, while inhibiting glycolysis in EPCs, which further decreased EPC stemness and promoted EPCs to a more active state toward differentiation, which may contribute to pathologic vascular formation. [Stem Cells] Abstract

mir526b and mir655 Promote Tumor Associated Angiogenesis and Lymphangiogenesis in Breast Cancer

miRNA-high cell free conditioned media promoted migration and tube formation by HUVECs, and upregulated VEGFR1, VEGFR2, and EP4 expression, showing paracrine stimulation of miRNA in the tumor microenvironment. The miRNA-induced migration and tube formation phenotypes were abrogated with EP4 antagonist or PI3K/Akt inhibitor treatments, confirming the involvement of the EP4 and PI3K/Akt pathway. [Cancers] Full Article

The Metalloproteinase ADAM15 Is Upregulated by Shear Stress and Promotes Survival of Endothelial Cells

Functionally, ADAM15 promoted survival of endothelial cells challenged by growth factor depletion or TNF stimulation as shown by ADAM15 shRNA knockdown. Exposure to shear stress increased endothelial survival while additional knockdown of ADAM15 reduced survival under flow conditions. [J Mol Cell Cardiol] Abstract | Graphical Abstract

A New Role for Host Annexin A2 in Establishing Bacterial Adhesion to Vascular Endothelial Cells: Lines of Evidence from Atomic Force Microscopy and an In Vivo Study

The authors employed a novel, anatomically based, in vivo quantitative bacterial-adhesion-to-vascular-endotheial cell (EC) system, combined with atomic force microscopy, to examine the role of endothelial luminal surface annexin a2 (ANXA2) during rickettsial adherence to ECs. They also examined whether ANXA2 antibody affected binding of Staphylococcus aureus to ECs. [Lab Invest] Abstract

Cohesive and Anisotropic Vascular Endothelial Cell Motility Driving Angiogenic Morphogenesis

To uncover hidden laws of integration driving angiogenic morphogenesis, researchers analyzed endothelial cell (EC) behaviors in an in vitro angiogenic sprouting assay using mouse aortic explants in combination with mathematical modeling. Time-lapse imaging of sprouts extended from EC sheets around tissue explants showed directional cohesive EC movements with frequent U-turns, which often coupled with tip cell overtaking. [Sci Rep] Full Article

Retinal Myeloid Cells Regulate Tip Cell Selection and Vascular Branching Morphogenesis via Notch Ligand Delta-Like 1

In vitro, co-culture of human endothelial cells (ECs) with monocyte-derived macrophages induced Delta-like (Dll) 1 upregulation in macrophages and Dll4 upregulation and an endothelial tip cell signature in ECs. Furthermore, culturing human ECs on recombinant DLL1 induced endothelial Dll4 expression and a tip cell program, indicating that changes were Dll1-dependent. [Sci Rep] Full Article

Periodontitis-Induced Systemic Inflammation Exacerbates Atherosclerosis Partly via Endothelial-Mesenchymal Transition in Mice

In vitro, Porphyromonas gingivalis lipopolysaccharide enhanced the secretion of pro-inflammatory cytokines from macrophages and increased the adhesion of monocytes to endothelial cells by upregulating the expression of adhesion molecules from endothelial cells. Moreover, secretory proteins, such as TNF-α, from macrophages induced endothelial-mesenchymal transitions of the endothelial cells. [Int J Oral Sci] Full Article

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Refueling the Ischemic CNS: Guidance Molecules for Vascular Repair

Besides the most intensively studied angiogenic growth factors, recent research has indicated that the process of vascular sprouting and migration also requires the participation of guidance molecules, many of which were initially identified as regulators of axonal growth. The authors review the inhibitory and growth-promoting effects of guidance molecules on the vascular system and discuss their potential as novel angiogenic targets for neurovascular diseases. [Trends Neurosci] Abstract

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

Hemostemix Announces Enrollment Update for the ACP-01 Phase II Critical Limb Ischemia Clinical Trial

Hemostemix Inc. announced that it has enrolled a total of forty patients in its continuing Phase II Clinical Trial for critical limb ischemia (CLI) to-date. The clinical trial is a randomized, placebo-controlled, double blind Phase II trial of the safety and efficacy of ACP-01 in patients with advanced CLI who have exhausted all surgical and medical treatment options. [Hemostemix Inc.] Press Release

Synergys Announces Second Phase I SBIR Funding from National Institutes of Health

Synergys Biotherapeutics announced the granting of its second Phase I Small Business Innovation Research (SBIR) award by the National Cancer Institute. This award will support the development for ovarian cancer an anti-HER2 antibody fusion candidate that contains a highly anti-angiogenic dimeric mutant endostatin as its fusion partner. [Synergys Biotherapeutics (Business Wire, Inc.)] Press Release

Pfizer Receives US FDA Approval for Its Oncology Biosimilar, ZIRABEV™ (Bevacizumab-Bvzr)

Pfizer Inc. announced the FDA has approved ZIRABEV™, a biosimilar to Avastin^®, for the treatment of five types of cancer: metastatic colorectal cancer; unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma; and persistent, recurrent or metastatic cervical cancer. [Pfizer Inc.] Press Release

Hungarian Government Takes Control of Research Institutes despite Outcry

After months of struggle between Hungary’s research ministry and its scientific community, the nation’s parliament ratified a law on 2 July that gives the government control over the 40 or so institutes belonging to the Hungarian Academy of Sciences. The government says that its aim is to make research more innovative. [Nature News] Editorial

Stem Cell Funding Agency CIRM Is Nearly Out of Funds

After funding stem cell research since 2004, the California Institute for Regenerative Medicine (CIRM) is running out of funds. The state agency currently has funding requests for $88 million pending but only $33 million left to give out to scientists. [The Scientist] Editorial

NEW EMBL Conference: Cancer Genomics
November 4-6, 2019
Heidelberg, Germany

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NEW Research Technician – 3D Vascularized In Vitro Tissue Development (European Molecular Biology Laboratory)

NEW Group Leader – Vascular Biology (Ludwig-Maximilians-University)

NEW Postdoctoral Researcher – Vascular Biology (Karolinska Institutet)

NEW Postdoctoral Fellow – Endothelial Cell Ion Channels (The University of Tennessee Health Science Center)

Postdoctoral Position – Vascular Research (University of Illinois-Chicago)

Faculty Positions – Cardiovascular Biomedical Research (Virginia Tech)

Postdoctoral Fellow – Endothelial Dysfunction in Inflammatory Disease (Seattle Children’s Hospital)

Assistant/Associate Professor – Vascular Physiology & Disease (Stanford Medicine)

Postdoctoral Fellowship – Neurovascular Imaging Research (University of Nevada)

Postdoctoral Fellow – Cardiovascular Diseases (Rutgers University)

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