Volume 1.05 | Apr 11

Newsletter Issue
Endothelial Cell News 1.05 April 11, 2016
Endothelial Cell News
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Somatic PIK3CA Mutations as a Driver of Sporadic Venous Malformations
PIK3CA mutations promote downstream signaling and proliferation in endothelial cells and impair normal vasculogenesis in embryonic development. Scientists successfully treated venous malformations in mouse models using pharmacological inhibitors of PI3Kα administered either systemically or topically. [Sci Transl Med] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Co-Option of Liver Vessels and Not Sprouting Angiogenesis Drives Acquired Sorafenib Resistance in Hepatocellular Carcinoma
While sorafenib initially inhibited angiogenesis and stabilized tumor growth, no angiogenic ‘rebound’ effect was observed during development of resistance unless therapy was stopped. Instead, resistant tumors became more locally infiltrative, which facilitated extensive incorporation of liver parenchyma and the co-option of liver-associated vessels. [J Natl Cancer Inst] Abstract | Press Release | Video

Targeting Soluble CD146 with a Neutralizing Antibody Inhibits Vascularization, Growth and Survival of CD146-Positive Tumors
The authors found that CD146 expression in cancer cells is associated with a secretion of soluble CD146 (sCD146) that constitutes an active player in tumor development. Indeed, sCD146 induced the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. [Oncogene] Abstract

A KSHV MicroRNA Enhances Viral Latency and Induces Angiogenesis by Targeting GRK2 to Activate the CXCR2/AKT Pathway
The authors demonstrated a role of miR-K12-3 (miR-K3) and its induced signal pathway in Kaposi’s sarcoma-associated herpesvirus (KSHV) latency and KSHV-induced angiogenesis. They found that overexpression of miR-K3 not only promoted viral latency by inhibiting viral lytic replication, but also induced angiogenesis. [Oncotarget] Full Article

Gap Junction-Mediated Transfer of miR-145-5p from Microvascular Endothelial Cells to Colon Cancer Cells Inhibits Angiogenesis
SW480 colon carcinoma cells form functional gap junction composed of connexin-43 with human microvascular endothelial cells (HMEC). When HMEC were loaded with microRNA (miR)-145-5p mimics, the miR-145 level drastically increased in SW480. [Oncotarget] Full Article

Mitochondria-Targeted Esculetin Alleviates Mitochondrial Dysfunction by AMPK-Mediated Nitric Oxide and SIRT3 Regulation in Endothelial Cells: Potential Implications in Atherosclerosis
Researchers synthesized a novel mitochondria-targeted esculetin (Mito-Esc) with an aim to investigate its effect during oxidative stress-induced endothelial cell death and angiotensin (Ang)-II-induced atherosclerosis in ApoE−/− mice. Mito-Esc but not natural esculetin treatment significantly inhibited H2O2– and Ang-II-induced cell death in human aortic endothelial cells by enhancing NO production via AMPK-mediated eNOS phosphorylation. [Sci Rep] Full Article

Implication of Long Noncoding RNAs in the Endothelial Cell Response to Hypoxia Revealed by RNA-Sequencing
To test the functional relevance of long noncoding RNAs in endothelial cells, knockdown of H19 expression was performed. H19 inhibition decreased human umbilical vein endothelial cell growth, inducing their accumulation in G1 phase of the cell cycle; accordingly, p21 expression was increased. [Sci Rep] Full Article

Prominin-1/CD133 Expression as Potential Tissue-Resident Vascular Endothelial Progenitor Cells in the Pulmonary Circulation
To determine whether Prominin-1/CD133 expression can be a marker of tissue-resident vascular endothelial progenitor cells in the pulmonary circulation, researchers examined the origin and characteristics of Prom1+Pulmonary vascular endothelial cells considering cell cycle status, viability, histological distribution, and association with pulmonary vascular remodeling. [Am J Physiol Lung Cell Mol Physiol] Abstract

Targeted Delivery of MicroRNA-126 to Vascular Endothelial Cells via REDV Peptide Modified PEG-Trimethyl Chitosan
A short peptide Arg-Glu-Asp-Val (REDV) was linked to trimethyl chitosan (TMC) via a bifunctional poly(ethylene glycol) (PEG) linker for the targeted delivery of microRNA-126 (miRNA-126) to vascular endothelial cells. The morphology, serum stability and cytotoxicity of the polyplex/miRNA complexes, namely, TMC/miRNA, TMC-g-PEG/miRNA and TMC-g-PEG-REDV/miRNA, were investigated along with the cellular uptake, proliferation and in vitro miRNA transfection efficiency. [Biomater Sci] Abstract

Interleukin-19 Induces Angiogenesis in the Absence of Hypoxia by Direct and Indirect Immune Mechanisms
IL-19 signaled through the IL-20 receptor complex, and IL-19 induced IL-20 receptor subunit expression in aortic rings and cultured human vascular smooth muscle cells, but not in endothelial cells, in a PPARγ-dependent mechanism. IL-19 activated STAT3 and IL-19 angiogenic activity in aortic rings was STAT3-dependent. [Am J Physiol Cell Physiol] Abstract

Pdgfrb-Cre Targets Lymphatic Endothelial Cells of both Venous and Non-Venous Origins
Researchers showed that Pdgfrb-Cre does not target yolk sac (YS) hemogenic endothelium or YS-derived erythro-myeloid progenitors. Instead, a high proportion of endothelial cells (ECs) in embryonic blood vessels of multiple organs, as well as venous derived lymphatic ECs were targeted. [Genesis] Abstract

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BM Aging: Implication for Cell Therapy with EPCs
The authors comprehensively discuss the age-related changes of bone marrow (BM) and endothelial progenitor cells (EPCs) and their implication for cardiovascular cell-therapies. They also examine alternative approaches under investigation to enhance EPC potency. [Mech Ageing Dev] Abstract

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Merck and Pfizer Announce First Patient Treated in Phase III Combination Study with Avelumab and INLYTA® in Renal Cell Carcinoma
Merck and Pfizer announced the treatment of the first patient in a Phase III study of avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in an advanced renal cell carcinoma setting. [Pfizer Inc.] Press Release

Jazz Pharmaceuticals Announces FDA Approval of Defitelio® (Defibrotide Sodium) for the Treatment of Hepatic Veno-Occlusive Disease (VOD) with Renal or Pulmonary Dysfunction following Hematopoietic Stem-Cell Transplantation (HSCT)
Jazz Pharmaceuticals plc announced that the United States Food and Drug Administration (FDA) granted marketing approval for Defitelio® for the treatment of adult and pediatric patients with hepatic VOD, also known as sinusoidal obstruction syndrome, with renal or pulmonary dysfunction following HSCT. [Jazz Pharmaceuticals plc] Press Release

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National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Cell Signaling in Cancer: From Mechanisms to Therapy
June 5-10, 2016
Snowmass Village, United States

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NEW Faculty Position (University of North Carolina at Chapel Hill)

Assistant/Associate Professor – Physiology and Biophysics (University of Illinois – Chicago)

Postdoctoral Scientist – Leukemia and Lymphoma (Max Delbruck Center for Molecular Medicine in the Helmholtz Association)

PhD Students and Postdoctoral Fellows – Neuroscience/Neurology (The Chinese University of Hong Kong)

Postdoctoral Fellow – Mechanoregulation of Fibrosis and Vascular Injury (St. Michael’s Hospital)

PhD Program – Cell Communication in Health and Disease (Medical University of Vienna)

Postdoctoral Positions – Tissue Repair/Inflammation (Institut Pasteur)

Postdoctoral Research Fellow – Angiogenesis and Metabolic Microenvironment Contributing to Carcinogenesis (Beth Israel Deaconess Medical Center – Harvard Medical School)

Postdoctoral Fellow – Ion Channel Signaling and Metabolism (University of Iowa Carver College of Medicine)

Postdoctoral Scientist – Isoprenoid Metabolism in Angiogenesis and Cancer (VIB)

Postdoctoral Fellow/Research Associate – Translational Genomics and Cancer Immunobiology & Immunotherapy (Children’s Hospital of Philadelphia)

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