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Ganga Gopinathan, Carla Milagre, Oliver M T Pearce, Louise E Reynolds, Kairbaan Hodivala-Dilke, David A Leinster, Haihong Zhong, Robert E Hollingsworth, Richard Thompson, James R Whiteford, Frances Balkwill
The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here, we show that IL6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared with VEGF-stimulated vessels. The mechanism of IL6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as angiopoietin2 (Ang2)...
August 1, 2015: Cancer Research
Béla Merkely, Edit Gara, Zsuzsanna Lendvai, Judit Skopál, Thomas Leja, Wenhua Zhou, Annamária Kosztin, György Várady, Maxime Mioulane, Zsolt Bagyura, Tamás Németh, Sian E Harding, Gábor Földes
Vascular derivatives of human embryonic stem cells (hESC) are being developed as sources of tissue-specific cells for organ regeneration. However, identity of developmental pathways that modulate the specification of endothelial cells is not known yet. We studied phosphatidylinositol 3-kinase (PI3K)-Forkhead box O transcription factor 1A (FOXO1A) pathways during differentiation of hESC toward endothelial lineage and on proliferation, maturation, and cell death of hESC-derived endothelial cells (hESC-EC). During differentiation of hESC, expression of FOXO1A transcription factor was linked to the expression of a cluster of angiogenesis- and vascular remodeling-related genes...
April 1, 2015: Stem Cells and Development
Yan-Wei Chen, Hong Yang, Hong Mou, Song-Lan Yang, You Zhang
Angiopoietin2( ANGPT2 ) plays an important role in tumor angiopoiesis. ANGPT2 antagonises ANGPT1 resulting in an effect on the stability of blood vessels, which promotes tumor growth, invasion, proliferation as well as relating to tumor vascular density. A lot of researches published papers about anti-ANGPT2 for the treatment of tumor, and have made some progresses. In this review, the role of ANGPT2 in the pathogenesis of acute myelogenous leukemia (AML), including its effects on proliferation of leukemia cells, bone marrow angiopoiesis, tumor invasion and metastasis are briefly summarised in order to provide the basis for targeted ANGPT2 in treatment of AML...
October 2014: Zhongguo Shi Yan Xue Ye Xue za Zhi
S J Lee, I Lee, J Lee, C Park, W K Kang
BACKGROUND: Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are commonly prescribed because of their therapeutic and preventive effects on cardiovascular diseases. Even though they have been occasionally reported to have antitumour activity, it is unknown whether statins have anti-angiogenic effect in human colorectal cancer (CRC). METHODS: A total of 11 human CRC cell lines were used to test the effects of bevacizumab, statins, and bevacizumab plus statins on human umbilical vein endothelial cell (HUVEC) viability and invasion in vitro...
July 29, 2014: British Journal of Cancer
Jimmy Masjkur, Ian Levenfus, Sven Lange, Carina Arps-Forker, Steve Poser, Nan Qin, Vladimir Vukicevic, Triantafyllos Chavakis, Graeme Eisenhofer, Stefan R Bornstein, Monika Ehrhart-Bornstein, Andreas Androutsellis-Theotokis
We present a method to efficiently culture primary chromaffin progenitors from the adult bovine adrenal medulla in a defined, serum-free monolayer system. Tissue is dissociated and plated for expansion under support by the mitogen basic fibroblast growth factor (bFGF). The cultures, although not homogenous, contain a subpopulation of cells expressing the neural stem cell marker Hes3 that also propagate. In addition, Hes3 is also expressed in the adult adrenal medulla from where the tissue is taken. Differentiation is induced by bFGF withdrawal and switching to Neurobasal medium containing B27...
July 2014: Stem Cells Translational Medicine
Tao Li, Zhiqiang Liu, Kesheng Jiang, Qin Ruan
Angiopoietin2 (Ang2) and its Tie2 receptor have extensive effects on tumor malignancy including angiogenesis and metastasis. In this study, we evaluated the protective effect of Ang2 on doxorubicin-induced apoptosis in HepG2 cells. Ang2 (400 ng/ml) attenuated doxorubicin-mediated cytotoxicity by upregulating the expression of Survivin and Ref-1, which was reversed by a soluble extracellular domain of Tie2. Mechanistic study showed Ang2 activated ERK-MSK cascade to induce histone H3 phosphorylation and inducible gene expression...
September 1, 2013: Cancer Letters
Xing Wen Gong, Jun Hua Mai, Yu Hong Xu
The angiopoietin-Tie2 binding and related signal transduction pathways are crucial for vascular angiogenesis, blood vessel integrity and maturation. In this study, we preformed a virtual screening of small molecules targeting to Tie2. The binding site was selected at the extracellular ligand binding region of Tie2, rather than its conventional endocellular ATP binding region. It was found that loperamide, a widely-used antidiarrhea drug, was among the top hits. The binding between loperamide and Tie2 was confirmed by surface plasmon resonance (SPR) assay...
April 1, 2012: Bioorganic & Medicinal Chemistry Letters
Adriana Albini, Douglas M Noonan
No abstract text is available yet for this article.
March 21, 2012: Journal of the National Cancer Institute
Xu Cui, Michael Chopp, Alex Zacharek, Xinchun Ye, Cynthia Roberts, Jieli Chen
We investigated the changes and the molecular mechanisms of cerebral vascular damage after stroke in type-2 diabetic (T2DM) mice. Adult male db/db T2DM and wild-type (WT) mice were subjected to transient middle cerebral artery occlusion (MCAo) and sacrificed 24 hours after MCAo. T2DM-mice exhibited significantly increased blood glucose, brain hemorrhagic rate, mortality and cerebrovascular density, but decreased cerebrovascular diameter, arteriolar density and arterial mural cell numbers in the ischemic brain compared with WT mice...
July 2011: Neurobiology of Disease
Jing Tian, Sohrab Fratz, Yali Hou, Qing Lu, Agnes Görlach, John Hess, Christian Schreiber, Sanjeev A Datar, Peter Oishi, John Nechtman, Robert Podolsky, Jin-Xiong She, Jeffrey R Fineman, Stephen M Black
Disordered angiogenesis is implicated in pulmonary vascular remodeling secondary to congenital heart diseases (CHD). However, the underlying genes are not well delineated. We showed previously that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an "angiogenesis burst" between 1 and 4 wk of age. Thus we hypothesized that the increased PBF elicited a proangiogenic gene expression profile before onset of vessel growth. To test this we utilized microarray analysis to identify genes that could be responsible for the angiogenic response...
January 1, 2011: Physiological Genomics
Ana Lúcia Cordeiro, António Figueiredo, Inês Tomada, Henrique de Almeida, Delminda Neves
Aging is the single most significant risk factor for erectile dysfunction (ED), leading to structural modification of cavernous tissue and altering expression of vascular growth factors. The angiopoietin/Tie2 system has been recently considered as a potential target for therapy of vascular disorders, including ED. Hence, the aim of this study was to analyze expression of angiopoietin1 (Ang1), angiopoietin2 (Ang2), and their receptor Tie2 in corpus cavernosum (CC) of rat during aging (6, 12, 18, and 24 months)...
December 2010: Microscopy and Microanalysis
Sangjin Lee, Tri M Bui Nguyen, Dmitry Kovalenko, Neeta Adhikari, Suzanne Grindle, Sean P Polster, Robert Friesel, Sundaram Ramakrishnan, Jennifer L Hall
Sprouty1 (Spry1) is a conserved antagonist of FGF signaling. The goal of this study was to further explore the downstream mechanisms governing Spry1 inhibition of endothelial cell proliferation. Up-regulation of Spry1 in HUVECs inhibited tube formation on Matrigel (n = 6, P < 0.001). This was associated with decreased proliferation as measured by BrdU incorporation (n = 6, P < 0.001) and increased protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A), p21 and cyclin-dependent kinase inhibitor 1B (CDKN1B), p27...
May 2010: Molecular and Cellular Biochemistry
Andreas Androutsellis-Theotokis, Maria A Rueger, Deric M Park, Haik Mkhikian, Erica Korb, Steve W Poser, Stuart Walbridge, Jeeva Munasinghe, Alan P Koretsky, Russel R Lonser, Ronald D McKay
In Parkinson's disease, multiple cell types in many brain regions are afflicted. As a consequence, a therapeutic strategy that activates a general neuroprotective response may be valuable. We have previously shown that Notch ligands support neural precursor cells in vitro and in vivo. Here we show that neural precursors express the angiopoietin receptor Tie2 and that injections of angiopoietin2 activate precursors in the adult brain. Signaling downstream of Tie2 and the Notch receptor regulate blood vessel formation...
August 11, 2009: Proceedings of the National Academy of Sciences of the United States of America
C Ellenberger, K Müller, H-A Schoon, S Wilsher, W R Allen
Anovulatory haemorrhagic follicles (AHFs) are often the reason for ovulation failure in the mare. As the underlying factors that lead to AHF development are not well understood, it was of interest to investigate the vascularization of AHFs compared with normal follicles and corpora lutea (controls). In the present study, the ovarian cell populations investigated immunohistochemically included granulosa and luteal cells as well as various vascular structures. None of these cell types showed differences in the expression of vascular endothelial growth factor A (VEGF-A) between control ovaries containing normal follicles and corpora lutea and ovaries with AHFs...
June 2009: Reproduction in Domestic Animals, Zuchthygiene
GuoHua Li, Wei Huang, QingJie Xia, KaiXuan Yang, RaoFang Liu, HuiLi Zhu, Wei Jiang
Decidualization is accompanied by extensive angiogenesis, which is an essential step in the maturation of new blood vessels in mammalian pregnancy. The purpose of this study was to determine a distribution of uNK cells (CD56(+) uNK or CD56(bright) cells) in human decidua of the first-trimester pregnancy, and investigate whether uNK cells in human decidua could express vascular endothelial growth factor (VEGF-A) and/or angiopoietin2 (Ang2). Our immunohistochemical staining results demonstrated that a great amount of uNK (CD56(+)) cells scattered throughout the decidual stroma and near endometrial gland and spiral vessels in human decidua...
February 2008: Science in China. Series C, Life Sciences
Koung Li Kim, In-Soon Shin, Jeong-Min Kim, Jin-Ho Choi, Jonghoe Byun, Eun-Seok Jeon, Wonhee Suh, Duk-Kyung Kim
OBJECTIVE: Ischemia-dependent upregulation of angiopoietin2 (Ang2) led us to hypothesize the potentially proangiogenic Ang2-Tie2 signaling in endothelial progenitor cells (EPCs). Given the well-known vascular destabilizing action of Ang2 in mature endothelium, we investigated the yet unidentified mechanism behind cell-dependent differential activity of Ang2. METHODS AND RESULTS: Both in vitro and in vivo experiments showed that Ang2 promoted angiogenicity of human cord blood-derived EPCs, where Ang2 directly activated Tie2 and its related downstream signaling molecules...
December 1, 2006: Cardiovascular Research
Sukriti Nag, Tripti Papneja, Roopa Venugopalan, Duncan J Stewart
Normal intracerebral and pial vessels show constitutive expression of angiopoietin (Ang) 1 in endothelium while weak Ang2 immunoreactivity is present in occasional vessels. In the early phase postinjury, blood-brain barrier (BBB) breakdown at the lesion site is associated with decreased endothelial Ang1 and increased Ang2 expression, raising the possibility that Ang2 may have a role in early BBB breakdown. In order to determine whether Ang2 can cause BBB breakdown, the effect of recombinant Ang2 on cerebrovascular permeability to horseradish peroxidase (HRP) was studied in normal rat cortex...
October 2005: Laboratory Investigation; a Journal of Technical Methods and Pathology
Stella Sarlos, Bishoy Rizkalla, Christina J Moravski, Zemin Cao, Mark E Cooper, Jennifer L Wilkinson-Berka
There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0-18...
September 2003: American Journal of Pathology
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