Endothelial Cell News Volume 2.11 | Apr 3 2017

TOP STORY

Mutual Regulation of Tumor Vessel Normalization and Immunostimulatory Reprogramming

Scientists showed that type 1 T helper cells play a crucial role in vessel normalization. Bioinformatic analyses revealed that gene expression features related to vessel normalization correlate with immunostimulatory pathways, especially T lymphocyte infiltration or activity. [Nature] Abstract | Press Release | Video

(Ranked by impact factor of the journal)

Modulation of Endothelial BMPR2 Activity by VEGFR3 in Pulmonary Arterial Hypertension

The authors utilized a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between VEGFR3 and bone morphogenetic protein type 2 receptors (BMPR2). Attenuation of Vegfr3 in zebrafish embryos abrogated Bmp2b-induced ectopic angiogenesis. [Circulation] Abstract

Long Noncoding RNA MANTIS Facilitates Endothelial Angiogenic Function

Researchers identified novel and functionally important endothelial long noncoding RNAs (lncRNAs). Their search for epigenetically controlled endothelial lncRNAs yielded lncRNA n342419, termed MANTIS, as the most strongly regulated lncRNA. [Circulation] Abstract | Full Article (Download)

On-Chip Human Microvasculature Assay for Visualization and Quantification of Tumor Cell Extravasation Dynamics

Investigators describe an in vitro model of the human microcirculation with the potential to recapitulate discrete steps of early metastatic seeding, including arrest, transendothelial migration and early micrometastases formation. [Nat Protoc] Abstract

Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance

Scientists indirectly monitored transcriptional activity of Yap1 and its spatiotemporal localization in living zebrafish and found that Yap1 entered the nucleus and promoted transcription in response to blood flow. In cultured human endothelial cells, laminar shear stress induced nuclear import of YAP and its transcriptional activity in a manner independent of Hippo signaling. [Dev Cell] Full Article | Graphical Abstract

Hsp90β Promoted Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma

The authors investigated the correlation between Hsp90β expression and CD31⁺ endothelial cell-dependent vessel density. Hsp90β promoted vascular endothelial growth factor receptors expression by increasing their promoter activities. The proliferation, migration, invasion, and tube formation activities of human endothelial cells significantly increased when Hsp90β was overexpressed. [Mol Cancer] Full Article

miRNA199a-3p Suppresses Tumor Growth, Migration, Invasion and Angiogenesis in Hepatocellular Carcinoma by Targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2

Scientists investigated the role of microRNA (miR)-199a-3p in the regulation of tumor microenvironment and development of hepatocellular carcinoma by several in vitro and in vivo assays. In vitro restoration of miR-199a-3p expression either in endothelial cells (ECs) or in cancer cells significantly diminished migration of ECs in co-culture assay. [Cell Death Dis] Full Article

miR-126 and miR-126* Regulate Shear-Resistant Firm Leukocyte Adhesion to Human Brain Endothelium

Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, the authors observed that reduction of endothelial microRNA (miR)-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary multiple sclerosis patient-derived PBMC firm adhesion. [Sci Rep] Full Article

Galectin-3 Interacts with the Cell Surface Glycoprotein CD146 (MCAM, MUC18) and Induces Secretion of Metastasis-Promoting Cytokines from Vascular Endothelial Cells

Researchers sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. [J Biol Chem] Abstract

Unraveling the Receptor-Ligand Interactions between Bladder Cancer Cells and the Endothelium Using AFM

Investigators report the expression of MUC1 and CD43 on bladder cancer cells (BCs), and demonstrated that these ligands interact with ICAM-1 to mediate cancer cell-endothelial cell adhesion in the case of the more invasive BCs. [Biophys J] Abstract

Anti-Angiogenesis for Cancer Revisited: Is There a Role for Combinations with Immunotherapy?

Given the recent success of immunotherapies, combinations of anti-angiogenics with immune checkpoint blockers have become an attractive strategy. However, implementing such combinations will require a better mechanistic understanding of their interaction. The authors focus on revisiting the concept of anti-angiogenesis in combination with immunotherapy as a strategy for cancer treatment. [Angiogenesis] Abstract

Evaluation of Endothelial Function by Flow-Mediated Dilation: A Comprehensive Review in Rheumatic Disease

Despite partially eclipsed by pulse wave velocity measure in the modern scientific literature, researchers provide a comprehensive overview and critically discuss the available data supporting flow-mediated dilation as a surrogate marker of endothelial function and, therefore, its potential role in predicting early atherosclerosis in patients with rheumatic diseases. [Arch Immunol Ther Exp (Warsz)] Abstract

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

Kadmon Presents Preclinical Data Supporting the Therapeutic Potential of ROCK Inhibition in Pulmonary Fibrosis

Kadmon Holdings, Inc. announced preclinical data demonstrating the importance of the Rho-associated coiled-coil kinase (ROCK) signaling pathway in the pathogenesis of pulmonary fibrosis, supporting the therapeutic potential of ROCK inhibition to treat the disease. [Press release from Kadmon Holdings, Inc. discussing research presented at the 2017 Keystone Symposia on Injury, Inflammation and Fibrosis, Snowbird] Press Release

Opthea Reports Positive Phase I/IIA Clinical Results for OPT-302 in Wet AMD

Opthea Limited announced positive results from its Phase I/IIA clinical trial of OPT-302, a novel VEGF-C/D ‘Trap’ therapy for wet age-related macular degeneration. [Opthea Limited] Press Release

AVEO Announces First Patient Dosed in Phase I/II TiNivo Trial of Tivozanib and Opdiv^® (Nivolumab) in Advanced RCC

AVEO Oncology announced that the first patient has been dosed in the Phase I/II AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo^®, in advanced renal cell carcinoma (RCC). [AVEO Oncology] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the five billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

Few U.S. Animal Inspections Are Being Posted

The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial

NEW GRKs and Arrestins: From Structure to Disease
June 11-16, 2017
Saxtons River, United States

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NEW Postdoctoral Position – Intersectional Genetics (VIB)

NEW Research Assistant Professor – Endothelial and Epithelial Barrier Function (University of Chicago)

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

Research Associate – Cell Biology (University of Bristol)

Doctoral Research Position – Infection Biology (The Leibniz Institute for Natural Product Research)

Postdoctoral Position – Bioinformatics (The National Center for Scientific Research)

PhD Student – Brain Vascular Biology (ETH Zurich)

Postdoctoral Research Position – Retinal Cell Biology (University of California, Davis)

Postdoctoral Fellows – Endothelial Cell Dysfunction (The University of Tennessee Health Science Center)

Postdoctoral Fellow – Stem Cell Biology (Northwestern University)

Postdoctoral Fellow – Cardiopulmonary Molecular Biology (Hannover Medical School)

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