Endothelial Cell News Volume 5.05 | Feb 10 2020

TOP STORY

The Guidance Receptor Plexin D1 Is a Mechanosensor in Endothelial Cells

Researchers showed that plexin D1 (PLXND1) had a role in mechanosensation and mechanically induced disease pathogenesis. PLXND1 was required for the response of endothelial cells to shear stress in vitro and in vivo and regulated the site-specific distribution of atherosclerotic lesions. [Nature] Abstract

(Ranked by impact factor of the journal)

Inhibition of Vascular Calcification by Inositol Phosphates Derivatized with Ethylene Glycol Oligomers

(OEG2)₂-IP4 potently stabilized calciprotein particle growth, consistently demonstrated low micromolar activity in different in vitro models of vascular calcification (VC), and largely abolished the development of VC in rodent models, while not causing toxicity related to serum calcium chelation. [Nat Commun] Full Article

Single-Cell Transcriptomics Identifies CD44 as a Marker and Regulator of Endothelial to Haematopoietic Transition

Using single-cell transcriptome analysis and antibody screening, investigators identified CD44 as a marker of endothelial to hematopoietic transition (EHT) enabling them to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros region. They provided a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which hematopoietic stem and progenitor cells emerged. [Nat Commun] Full Article

BMP9 Signaling Promotes the Normalization of Tumor Blood Vessels

BMP9 overexpression in Lewis Lung Carcinoma (LLC) tumors significantly delayed tumor growth. Blood vessels in BMP9-overexpressing LLC tumors displayed markers of vascular maturation and were characterized by increased perivascular cell coverage. [Oncogene] Full Article

HIPK2 Suppresses Tumor Growth and Progression of Hepatocellular Carcinoma Through Promoting the Degradation of HIF-1α

Both in vitro and in vivo, HIPK2 inhibited the migration of HCC cells, as well as tumor growth and metastasis in xenograft and orthotopic syngeneic hepatocellular carcinoma (HCC) mouse models. Furthermore, HIPK2 inhibited the angiogenesis in HCC tumors. [Oncogene] Full Article

Beta Secretase 1-Dependent Amyloid Precursor Protein Processing Promotes Excessive Vascular Sprouting Through NOTCH3 Signaling

The authors report that increased endothelial sprouting in human-amyloid precursor protein (APP) transgenic mouse tissue was dependent on β-secretase processing of APP. Higher levels of amyloid beta peptides processing in TgCRND8 tissue coincided with decreased NOTCH3/JAG1 signalling, overproduction of endothelial filopodia and increased numbers of vascular pericytes. [Cell Death Dis] Full Article

α-Linolenic Acid but Not Linolenic Acid Protects against Hypertension: Critical Role of SIRT3 and Autophagic Flux

Researchers showed that α-linolenic acid but not linolenic acid supplementation alleviated systolic blood pressure elevation and improved ACh-induced, endothelium-dependent vasodilation in both spontaneously hypertensive rats (SHRs) and AngII-induced hypertensive mice [Cell Death Dis] Full Article

Developing a Xenograft Model of Human Vasculature in the Mouse Ear Pinna

Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. The authors demonstrated that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. [Sci Rep] Full Article

Production and Control of Coagulation Proteins for Factor X Activation in Human Endothelial Cells and Fibroblasts

Human dermal fibroblasts were used as comparator cells. Transcription factor (TF), FVII, FIX, FX, and prothrombin were detected in endothelial cells, and TF, coagulation factor (F)VII, FIX, and FX were detected in fibroblasts. In addition, FVII, FIX, FX, and prothrombin were detected by fluorescent microscopy in endothelial cells cytoplasm. [Sci Rep] Full Article

Conjugated Polymers Optically Regulate the Fate of Endothelial Colony Forming Cells

Researchers demonstrated that polymer-mediated optical excitation induced a robust enhancement of proliferation and lumen formation in vitro. They identified the underlying biophysical pathway as due to light-induced activation of TRPV1 channel. [Biophys J] Abstract

Perpendicular Alignment of Lymphatic Endothelial Cells in Response to Spatial Gradients in Wall Shear Stress

Investigators observed that lymphatic endothelial cells replicated aspects of the early steps in valvulogenesis: cells oriented perpendicular to flow in the region of maximum wall shear stress and exhibited enhanced nuclear localization of FOXC2, a transcription factor required for valvulogenesis. [Commun Biol] Full Article

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Checkpoint Inhibitor Immunotherapy in Kidney Cancer

Data has led to approvals of combination strategies of immune checkpoint inhibition plus agents that target the vascular endothelial growth factor receptor and a shift in the current standard of renal cell carcinoma care. However, controversies remain regarding the optimal therapy selection and treatment strategy for individual patients, which might be eventually overcome by current intensive efforts in biomarker research. [Nat Rev Urol] Abstract

Long Noncoding RNAs as Novel Players in the Pathogenesis of Hypertension

The authors summarize the current studies of long non-coding (lnc)RNAs in the pathogenesis of hypertension in order to aid in better understanding the molecular mechanism of hypertension and provide a basis to explore new therapeutic targets. [Hypertens Res] Abstract

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

Alkahest Initiates a Phase II Clinical Trial of AKST4290 in Parkinson’s Disease with Funding From the Michael J. Fox Foundation

Alkahest, Inc. announced the dosing of the first patient in a Phase II clinical trial of AKST4290, an orally administered CCR3 inhibitor, for treatment of Parkinson’s disease. The trial, AKST4290-211, is funded in part by The Michael J. Fox Foundation for Parkinson’s Research and will evaluate the effect of AKST4290 on motor function and activities of daily living in patients with Parkinson’s disease. [Alkahest, Inc.] Press Release

Researchers to Investigate Method of Growing New Blood Vessels

A potential new treatment is to increase the blood flow to damaged heart tissue by using drugs that encourage the body to grow new blood vessels. The project will be led by Professor Paolo Madeddu, Chair of Experimental Cardiovascular Medicine at the University of Bristol, who, along with his team, discovered that an excess of a protein called BACH1 can prevent blood vessel formation. [University of Bristol] Press Release

Trump’s 2021 Budget Drowns Science Agencies in Red Ink, Again

It’s another sea of red ink for federal research funding programs in President Donald Trump’s latest budget proposal. The 2021 budget request to Congress released February 10^th calls for deep, often double-digit cuts to R&D spending at major science agencies. [ScienceInsider] Editorial

Major Cancer Institute Sued by Its Own Researchers Over ‘Tapering’ Funding

Alleging that a leading cancer funder is slashing their support in an “unethical and reckless” way, six prominent cancer researchers at the University of California, San Diego, have filed a lawsuit to compel it to continue its current level of support. [ScienceInsider] Editorial

NEW First International STEMNET Meeting
May 6-8, 2020
Padua, Italy

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

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

NEW Postdoctoral Researcher – Microvascular Injury (University Hospital Carl Gustav Carus Dresden)

Postdoctoral Researcher – Human Atherosclerosis (Karolinska Institutet)

PhD Position – Aging (Lausanne University Hospital)

Postdoctoral Fellow – Vascular Dysfunction in Neurodegeneration (Lund University)

Postdoctoral Researcher (University of Illinois at Chicago)

Tenure Track Faculty – Endothelial Cell Regeneration (Ohio State University)

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

Postdoctoral Research Fellow – Pulmonary Vascular Diseases (Boston Children’s Hospital)

PhD Student – Aortic Disease (University Hospital of Cologne)

Postdoctoral Positions – Bioinformatics and Vascular Biology (KU Leuven)

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