Endothelial Cell News Volume 5.07 | Mar 2 2020

TOP STORY

Generation of Human Endothelium in Pig Embryos Deficient in ETV2

Scientists used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

Wnt-Mediated Endothelial Transformation into Mesenchymal Stem Cell-Like Cells Induces Chemoresistance in Glioblastoma

Researchers identified a c-Met-mediated axis that induced β-catenin phosphorylation at Ser⁶⁷⁵ and Wnt signaling activation, inducing multidrug resistance-associated protein-1 expression and leading to endothelial cell (EC) stemness-like activation and chemoresistance. Genetic ablation of β-catenin in ECs overcame glioblastoma tumor resistance to temozolomide chemotherapy in vivo. [Sci Transl Med] Abstract | Press Release

Vascular Endothelium-Targeted Sirt7 Gene Therapy Rejuvenates Blood Vessels and Extends Life Span in a Hutchinson-Gilford Progeria Model

The authors generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome Lmna^G609G mutation, called progerin. The Lmna^f/f;TC mice with progerin expression induced by Tie2-Cre exhibited defective microvasculature and neovascularization, accelerated aging, and shortened life span. [Sci Adv] Full Article

Hydrogel Cross-Linking-Programmed Release of Nitric Oxide Regulates Source-Dependent Angiogenic Behaviors of Human Mesenchymal Stem Cell

Investigators used a gelatin hydrogel that released nitric oxide (NO) upon crosslinking by a transglutaminase reaction. Then, the source-specific behaviors of bone marrow versus adipose tissue-derived human mesenchymal stem cells were monitored in the NO gels. NO inhibition resulted in significant decreases in their angiogenic activities. [Sci Adv] Full Article

Autophagic Degradation of HAS2 in Endothelial Cells: A Novel Mechanism to Regulate Angiogenesis

Researchers discovered that HAS2 was degraded in vascular endothelial cells via autophagy evoked by nutrient deprivation, mTOR inhibition, or pro-autophagic proteoglycan fragments endorepellin and endostatin. Using live-cell and super-resolution confocal microscopy, they found that protracted autophagy evoked a dynamic interaction between HAS2 and ATG9A, a key transmembrane autophagic protein. [Matrix Biol] Full Article

miR-629-5p Promotes the Invasion of Lung Adenocarcinoma via Increasing Both Tumor Cell Invasion and Endothelial Cell Permeability

Scientists showed a significantly positive correlation between miR-629-5p level and tumor invasion in lung adenocarcinom (LUAD) specimens. In a human LUAD metastasis mouse model, H1650 cells were more aggressive than A549 cells in vivo, including higher incidence of vascular invasion and pulmonary colonization. [Oncogene] Abstract

Functional Angiogenesis Requires Microenvironmental Cues Balancing Endothelial Cell Migration and Proliferation

The authors multiplexed an established angiogenesis-on-a-chip platform that afforded higher throughput investigation of 3D endothelial cell sprouting emanating from a parent vessel through defined biochemical gradients and extracellular matrix. They found that two fundamental endothelial cell functions, migration and proliferation, dictated endothelial cell invasion as single cells vs. multicellular sprouts. [Lab Chip] Abstract | Graphical Abstract

c-Src Controls Stability of Sprouting Blood Vessels in the Developing Retina Independently of Cell-Cell Adhesion Through Focal Adhesion Assembly

Researchers identified an unexpected role for spatiotemporal c-Src activity in sprouting angiogenesis in the retina, which was in contrast to the dominant focus on c-Src’s role in maintenance of vascular integrity. Thus, mice specifically deficient in endothelial c-Src displayed significantly reduced blood vessel sprouting and loss in actin-rich filopodial protrusions at the vascular front of the developing retina. [Development] Abstract

PDK1 Promotes Ovarian Cancer Metastasis by Modulating Tumor-Mesothelial Adhesion, Invasion, and Angiogenesis via α5β1 Integrin and JNK/IL-8 Signaling

Scientists demonstrated high expression of the mitochondrial gatekeeping enzyme, pyruvate dehydrogenase kinase 1 (PDK1), in both clinical samples and cell lines of ovarian cancer. PDK1 expression was significantly associated with metastasis, reduced chemosensitivity, and poor overall and disease-free survival, and further highlighted as an independent prognostic factor. [Oncogenesis] Full Article

Combining Transcatheter Arterial Embolization with Iodized Oil Containing Apatinib Inhibits HCC Growth and Metastasis

Investigators simulated the changing of tumor microenvironment before and after transcatheter arterial embolization both in vitro and in vivo models. The anti-angiogenic effect of Apatinib was explored by bioassays in HUVECs, including cell migration, invasion and apoptosis, tube formation, and wound healing. [Sci Rep] Full Article

VEGF and bFGF Induction by Nitric Oxide Is Associated with Hyperbaric Oxygen-Induced Angiogenesis and Muscle Regeneration

Reactive oxygen species (ROS) upregulation was a key mechanism of hyperbaric oxygen, which produced high O₂ content in tissues through increased dissolution of oxygen at high pressure. Nitric oxide, a type of ROS, generally stabilized hypoxia-inducible factor 1α and stimulated secretion of VEGF and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induced angiogenesis. [Sci Rep] Full Article

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Vitamin D and Endothelial Function

Under pathogenic conditions, the oxidative stress caused by excessive production of reactive oxygen species (ROS) facilitates nitric oxide (NO) degradation and suppresses NO synthesis, consequently reducing NO bioavailability. Vitamin D, however, counteracts the activity of nicotinamide adenine dinucleotide phosphate oxidase, which produces ROS, and improves antioxidant capacity by enhancing the activity of antioxidative enzymes such as superoxide dismutase. [Nutrients] Full Article | Graphical Abstract

A Review on Anti-Cancer Properties of Quercetin in Breast Cancer

The authors identify the critical properties of Quercetin such as anti-inflammatory and anti-oxidant properties, and even its effects on proliferation, angiogenesis, or apoptosis that are considered anti-tumor properties to enhance breast cancer treatment. [Life Sci] Abstract | Graphical Abstract

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

Exelixis Announces First 100 Patients Enrolled in Phase III COSMIC-311 Pivotal Trial of Cabozantinib in Relapsed Radioiodine-Refractory Differentiated Thyroid Cancer

Exelixis, Inc. a Phase III pivotal trial evaluating cabozantinib versus placebo in patients with radioactive iodine-refractory differentiated thyroid cancer who have progressed after up to two VEGF receptor-targeted therapies. [Exelixis, Inc.] Press Release

Health Research Projects Receive Federal Funding

Eight research projects led by faculty members of the Rady Faculty of Health Sciences have received project grants from the Canadian Institutes of Health Research, totalling $3.8 million in support. “Congratulations to the [University of Manitoba] applicants who were successful in this highly competitive national funding process,” said Dr. Peter Nickerson, vice-dean research of the Rady Faculty of Health Sciences. [University of Manitooba] Press Release

China Bans Cash Rewards for Publishing Papers

Chinese institutions have been told to stop paying researchers bonuses for publishing in journals, as part of a new national policy to cut perverse incentives that encourage scientists to publish lots of papers rather than focus on high-impact work. [Nature News] Editorial

UC Santa Cruz Fires Graduate Students Taking Part in Strike

The University of California, Santa Cruz, fired 54 graduate student employees from their teaching positions on February 28, in the latest escalation of a months-long dispute over student pay, the Santa Cruz Sentinel reports. [The Scientist] Editorial

NEW Gordon Research Conference: Tissue Stem Cell Regulation by Autonomous and Non-Autonomous Mechanisms
July 12-17, 2020
Ventura, California, United States

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

NEW Postdoctoral Researcher – Endothelial Mechanotransduction (KU Leuven)

NEW Postdoctoral Researchers – Pancreatic-Endothelial Cell Interactions (German Research Center for Environmental Health)

NEW Research Associate – Blood Vessel Formation (The University of Manchester)

Research Fellow – Vascular Biology (Queen’s University Belfast)

Postdoctoral Fellowship – Endothelial Injury in Type 2 Diabetes (Karolinska Institutet)

PhD Candidate – Autoimmunity and Kidney Diseases (Radboud University Medical Centre)

Career Scientist – Neurosurgery and Regenerative Medicine (Mayo Clinic)

Postdoctoral Researcher – Neurodegeneration and Vascular Functions (Icahn School of Medicine at Mount Sinai)

PhD Position – Aging (Lausanne University Hospital)

Post-Doctoral Fellow – Metabolic Regulation of Vascular Formation (Oklahoma Medical Research Foundation)

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