Endothelial Cell News Volume 2.28 | Aug 21 2017

TOP STORY

Dasatinib Reversibly Disrupts Endothelial Vascular Integrity by Increasing Non-Muscle Myosin II Contractility in a ROCK-Dependent Manner

Dasatinib is a short-acting dual ABL/SRC family tyrosine kinase inhibitor (TKI), which is frequently used to treat chronic myeloid leukemia. The effects of TKIs on endothelial cells (ECs) were studied by various assays, such as real-time cell impedance measurements, live-cell microscopy, wound healing, western blot and an in vivo model. Dasatinib uniquely caused a profound, dose-dependent disorganization of the EC monolayers. [Clin Cancer Res] Abstract | Full Article

(Ranked by impact factor of the journal)

An Engineered S1P Chaperone Attenuates Hypertension and Ischemic Injury

Scientists report the development of a soluble carrier for sphingosine 1-phosphate (S1P), apolipoprotein M (ApoM)-Fc, which activated S1P receptors in a sustained manner and promoted endothelial function. In contrast, ApoM-Fc did not modulate circulating lymphocyte numbers, suggesting that it specifically activated endothelial S1P receptors. [Sci Signal] Abstract

Discovery of a ROCK Inhibitor, FPND, Which Prevents Cerebral Hemorrhage through Maintaining Vascular Integrity by Interference with VE-Cadherin

In vitro enzyme-based assays revealed that a new compound (FPND) with a novel scaffold identified by docking-based virtual screening could inhibit ROCK1 specifically at low micromolar concentration. Molecular modeling showed that FPND preferentially interacted with ROCK1, and the difference between the binding affinity of FPND toward ROCK1 and ROCK2 primarily resulted from non-polar contributions. [Cell Death Dis] Full Article

Up-Regulation of NADPH Oxidase-Mediated Redox Signaling Contributes to the Loss of Barrier Function in KRIT1 Deficient Endothelium

Investigators showed that endothelial reactive oxygen species production directly contributes to the loss of barrier function in KRIT1 deficient animals and cells, as targeted antioxidant enzymes reversed the increase in permeability in KRIT1 heterozygous mice as shown by intravital microscopy. [Sci Rep] Full Article

Suppression of GRK2 Expression Reduces Endothelial Dysfunction by Restoring Glucose Homeostasis

Scientists identified G-protein-coupled receptor kinase 2 (GRK2) as a novel therapeutic target of diabetic endothelial dysfunction and investigated the effect on diabetic endothelial dysfunction through the systemic administration of GRK2 siRNA using a hydrodynamic-based procedure, resulting in suppression of increased GRK2 protein levels in the liver. [Sci Rep] Full Article

PPARα Agonist Stimulated Angiogenesis by Improving Endothelial Precursor Cell Function via a NLRP3 Inflammasome Pathway

Researchers tested the hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin-induced diabetic mice. Compared with the untreated diabetic mice, wound closure and capillary densities were significantly increased in fenofibrate treated group. [Cell Physiol Biochem] Full Article

Tumor Microenvironment Conditions Alter Akt and Na⁺/H⁺ Exchanger NHE1 Expression in Endothelial Cells More than Hypoxia Alone: Implications for Endothelial Cell Function in Cancer

The authors compared the effects of hypoxia and tumor microenvironment (TME) conditions on regulation of the Na⁺/H⁺ exchanger NHE1, Ser/Thr kinases Akt1–3, and downstream effectors in endothelial cells. NHE1 and Akt were downregulated by TME conditions, more potently than by hypoxia alone. [BMC Cancer] Full Article

Effects of Fullerenols on Mouse Brain Microvascular Endothelial Cells

Scientists investigated whether the treatment of primary mouse brain microvascular endothelial cells with fullerenols impacts basal and inflammatory blood–brain barrier properties in vitro. [Int J Mol Sci] Full Article

Perinatal Testosterone Exposure Potentiates Vascular Dysfunction by ERβ Suppression in Endothelial Progenitor Cells

Preliminary results showed that perinatal testosterone exposure in mice induced estrogen receptor β (ERβ) suppression in endothelial progenitor cells in offspring but not in mothers, while estradiol had no effect. Further investigation showed that ERβ suppression is due to perinatal testosterone exposure-induced epigenetic changes with altered DNA methylation on the ERβ promoter. [PLoS One] Full Article

Effect of Micro Strain Stress on Proliferation of Endothelial Progenitor Cells In Vitro by the MAPK-ERK1/2 Signaling Pathway

Investigators report the effect of micro strain stress on proliferation of endothelial progenitor cells (EPCs) in vitro by loading different types of micro strain stress on EPCs. The results of flow cytometry showed that appropriate micro strain stress can promote EPC proliferation. [Biochem Biophys Res Commun] Abstract

TRPC3-Mediated Ca²⁺ Signals as a Promising Strategy to Boost Therapeutic Angiogenesis in Failing Hearts: The Role of Autologous Endothelial Colony Forming Cells

The authors discuss how VEGF uses repetitive Ca²⁺ spikes to regulate angiogenesis in endothelial colony forming cells (ECFCs) and outline how VEGF-induced intracellular Ca²⁺ oscillations differ between the two ECFC subtypes. [J Cell Physiol] Abstract

A Review of Anti-Angiogenic Targets for Monoclonal Antibody Cancer Therapy

Researchers highlight the role and relevance of VEGF and other potential therapeutic targets and their receptors in angiogenesis. They also cover the current status of monoclonal antibodies being developed to target these candidates for cancer therapy. [Int J Mol Sci] Full Article

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

CPRIT Awards $13M for Prevention, Research, Recruitment

Researchers in the NCI-designated Dan L Duncan Comprehensive Cancer Center have received $13,107,956 from the Cancer Prevention and Research Institute of Texas (CPRIT) for six new grants focused on evidence-based cancer prevention services, the recruitment of an established investigator, individual investigator and early translational research and core facility support. [Baylor College of Medicine] Press Release

Exelixis Submits U.S. Supplemental New Drug Application for CABOMETYX^® (Cabozantinib) for the Treatment of Previously Untreated Advanced Kidney Cancer

Exelixis, Inc. announced it has completed the submission of a supplemental New Drug Application to the FDA for CABOMETYX^® tablets as a treatment for patients with previously untreated advanced renal cell carcinoma. [Exelixis, Inc.] Press Release

NSF Reiterates Policy on Teaching Good Research Habits despite Its Limitations

The National Science Foundation (NSF) in Arlington, Virginia, has decided to double down on its implementation of a congressionally mandated policy aimed at reducing research misconduct among NSF-funded scientists, despite a new report that notes problems with the agency’s approach. [ScienceInsider] Editorial

Trump Offers His First List of Science Priorities, and It’s America First

President Donald Trump has translated his campaign promise to “make America great again” into his administration’s first blueprint for federal investment in science and technology. [ScienceInsider] Editorial

NEW Asia Pacific Vascular Biology Organization (APVBO) Conference 2017
November 17-20, 2017
Guangzhou, China

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

NEW Postdoctoral Fellowship – Smooth Muscle and Endothelial Function (University of Iowa)

NEW Postdoctoral Position – Vascular Biology Relating to Cardiovascular Diseases (University of Hawaii)

NEW Postdoctoral Position – Biology of Blood Platelets (INSERM)

Postdoctoral Fellow – Childhood Cardiovascular and Pulmonary Disease (University of Colorado Anschutz Medical Campus)

Postdoctoral Fellow – Structural Biology (Karolinska Institutet)

Tenure-Track Faculty Scientist (Temple University)

Assistant Professor – Stem Cell and Regenerative Medicine (Harvard University)

Postdoctoral Research Scientist – Tissue Repair (The University of Alabama)

Postdoctoral Research Scientist – Drug Discovery and Cell Therapy (Inserm)

Assistant Professor – Vascular and Microvascular Biophysics (Western University)

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