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https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#1
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27917461/intussusceptive-angiogenesis-and-expression-of-tie-receptors-during-porcine-metanephric-kidney-development
#2
Anastasia Logothetidou, Tim Vandecasteele, Els Van Mulken, Kimberley Vandevelde, Pieter Cornillie
Intussusceptive angiogenesis (IA) is required for normal embryonic vascular development. The Tie family of receptors and their ligands, the angiopoietins, play an important role in the growth or regression of blood vessels which are important not only during development but also throughout an organism's life. The presence of IA was investigated in glomerular capillaries of the fetal porcine metanephros using Mercox II resin casts. The first signs of IA were observed in stage III glomeruli. Stage IV and V glomeruli showed numerous signs of aligned pillar formation and their successive merging to delineate the vascular entities...
December 5, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27914241/engot-ov-6-trinova-2-randomised-double-blind-phase-3-study-of-pegylated-liposomal-doxorubicin-plus-trebananib-or-placebo-in-women-with-recurrent-partially-platinum-sensitive-or-resistant-ovarian-cancer
#3
Christian Marth, Ignace Vergote, Giovanni Scambia, Willi Oberaigner, Andrew Clamp, Regina Berger, Christian Kurzeder, Nicoletta Colombo, Peter Vuylsteke, Domenica Lorusso, Marcia Hall, Vincent Renard, Sandro Pignata, Rebecca Kristeleit, Sevilay Altintas, Gordon Rustin, Robert M Wenham, Mansoor Raza Mirza, Peter C Fong, Amit Oza, Bradley J Monk, Haijun Ma, Florian D Vogl, Bruce A Bach
AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m(2) once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo...
November 30, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27882546/human-gingival-fibroblasts-induced-and-differentiated-into-vascular-endothelial-like-cells
#4
Xuqian Liu, Jie Wang, Fusheng Dong, Hexiang Li, Yali Hou
A novel method for repair of vascular disease, mechanical damage, and tissue rebuilding is urgently required. Vascular endothelial cells (VECs) play an essential role in vascular rebuilding and vasotransplantation. In the present study, human gingival fibroblasts (HGFs) were cultured and induced into endothelial-like cells in vitro in order to confirm that HGFs with stem cell properties possessed the potential for differentiation into endothelial-like cells. The epithelium was extracted from normal human gingiva consisting of epithelium and connective tissue, which was isolated from patients...
November 24, 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27868196/differential-regulation-of-blood-flow-induced-neovascularisation-and-mural-cell-recruitment-by-vegf-and-angiopoietin-signalling
#5
Oliver A Stone, James G Carter, P Charles Lin, Ewa Paleolog, Maria J C Machado, David O Bates
Signalling through VEGF receptors and the Tie2 receptor by angiopoietins is required in combination with blood flow for the formation of a functional vascular network. We tested the hypothesis that VEGF and Ang1 contribute differentially to neovascularization induced by nitric oxide (NO) mediated vasodilatation, by comparing the phenotype of new microvessels in the mesentery during induction of vascular remodelling by over-expression of endothelial nitric oxide synthase (eNOS) in the fat pad of the adult rat mesentery during inhibition of Angiopoietin signalling with soluble Tie2 and VEGF signalling with sFlt1...
November 21, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27842980/establishment-characterization-and-long-term-culture-of-human-endocrine-pancreas-derived-microvascular-endothelial-cells
#6
Valeria Sordi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Erica Dugnani, Silvia Pellegrini, Rita Nano, Lorenza Pecciarini, Augusto Pessina, Luisa Pascucci, Lorenzo Piemonti, Giulio Alessandri
BACKGROUND: In vitro primary cultures of microvascular endothelial cells from endocrine pancreas are difficult to obtain, but can be a very helpful tool for studies of islet biology, transplantation and regenerative medicine. METHODS: We applied a protocol recently described for the isolation and culture of brain microvascular endothelial cells (EC) on human pancreatic islets. EC obtained were characterized in terms of morphological (light and transmission electron microscopy), phenotypical (by immunofluorescence and flow cytometry) and functional (cord formation assay and protein secretion by multiplex bead-based assay) characteristics...
November 11, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27798027/possible-role-of-il-6-and-tie2-gene-polymorphisms-in-predicting-the-initial-high-transport-status-in-patients-with-peritoneal-dialysis-an-observational-study
#7
Li Ding, Xinghua Shao, Liou Cao, Wei Fang, Hao Yan, Jiaying Huang, Aiping Gu, Zanzhe Yu, Chaojun Qi, Xinbei Chang, Zhaohui Ni
OBJECTIVES: The aim of this study was to investigate the effect of interleukin (IL)-6 and TIE2 gene polymorphisms on baseline peritoneal transport property. DESIGN: An observational study. SETTING: Renji Hospital in Shanghai, China. PARTICIPANTS: This study included 220 patients with continuous ambulatory peritoneal dialysis (PD). OUTCOME MEASURES: Patients were divided into 2 groups based on the results of an initial peritoneal equilibration test performed within 3 months of starting PD therapy: group 1 consisted of low/low average transporters (n=123), and group 2 consisted of high/high average transporters (n=97)...
October 26, 2016: BMJ Open
https://www.readbyqxmd.com/read/27778249/targeting-tie2-for-treatment-of-diabetic-retinopathy-and-diabetic-macular-edema
#8
Peter A Campochiaro, Kevin G Peters
Tie2 is a tyrosine kinase receptor located predominantly on vascular endothelial cells that plays a central role in vascular stability. Angiopoietin-1 (Angpt1), produced by perivascular cells, binds, clusters, and activates Tie2, leading to Tie2 autophosphorylation and downstream signaling. Activated Tie2 increases endothelial cell survival, adhesion, and cell junction integrity, thereby stabilizing the vasculature. Angiopoietin-2 (Angpt2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) are negative regulators increased by hypoxia; they inactivate Tie2, destabilizing the vasculature and increasing responsiveness to vascular endothelial growth factor (VEGF) and other inflammatory cytokines that stimulate vascular leakage and neovascularization...
December 2016: Current Diabetes Reports
https://www.readbyqxmd.com/read/27767064/angiopoietin-2-attenuates-angiotensin-ii-induced-aortic-aneurysm-and-atherosclerosis-in-apolipoprotein-e-deficient-mice
#9
Hongyou Yu, Corey S Moran, Alexandra F Trollope, Lynn Woodward, Robert Kinobe, Catherine M Rush, Jonathan Golledge
Angiogenesis and inflammation are implicated in aortic aneurysm and atherosclerosis and regulated by angiopoietin-2 (Angpt2). The effect of Angpt2 administration on experimental aortic aneurysm and atherosclerosis was examined. Six-month-old male apolipoprotein E deficient (ApoE(-/-)) mice were infused with angiotensin II (AngII) and administered subcutaneous human Fc-protein (control) or recombinant Angpt2 (rAngpt2) over 14 days. Administration of rAngpt2 significantly inhibited AngII-induced aortic dilatation and rupture of the suprarenal aorta (SRA), and development of atherosclerosis within the aortic arch...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27758887/tie2-expression-on-macrophages-is-required-for-blood-vessel-reconstruction-and-tumor-relapse-after-chemotherapy
#10
Lin Chen, Jie Li, Fei Wang, Chengliang Dai, Fan Wu, Xiaoman Liu, Taotao Li, Rainer Glauben, Yi Zhang, Guangjun Nie, Yulong He, Zhihai Qin
Tumor relapse after chemotherapy is a major hurdle for successful cancer therapy. Chemotherapeutic drugs select for resistant tumor cells and reshape tumor microenvironment, including the blood supply system. Using animal models, we observed on macrophages in tumor tissue a close correlation between upregulated Tie2 expression and tumor relapse upon chemotherapy. Conditional deletion of Tie2 expression in macrophages significantly prohibited blood supply and regrowth of tumors. Tie2(+) macrophages were derived from tumor-infiltrating Tie2(-)CD11b(+) cells and hypoxia-induced Tie2 expression on these cells...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27757426/tie2-mediated-tyrosine-phosphorylation-of-h4-regulates-dna-damage-response-by-recruiting-abl1
#11
Mohammad B Hossain, Rehnuma Shifat, David G Johnson, Mark T Bedford, Konrad R Gabrusiewicz, Nahir Cortes-Santiago, Xuemei Luo, Zhimin Lu, Ravesanker Ezhilarasan, Erik P Sulman, Hong Jiang, Shawn S C Li, Frederick F Lang, Jessica Tyler, Mien-Chie Hung, Juan Fueyo, Candelaria Gomez-Manzano
DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier...
April 2016: Science Advances
https://www.readbyqxmd.com/read/27754101/os-21-06-three-month-exposure-to-endothelin-1-overexpression-increases-blood-pressure-and-causes-small-artery-injury
#12
Pierre Paradis, Suellen C Coelho, Sofiane Ouerd, Júlio C Fraulob-Aquino, Stefan Offermanns, Ernesto L Schiffrin
OBJECTIVE: The mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Recently, we developed a transgenic mouse with tamoxifen-inducible endothelium-restricted human ET-1 overexpression (ieET-1) using Cre/loxP technology. ieET-1 mice exhibited a BP increase after three weeks of induction in an ET type A receptor-dependent manner, in absence of evident vascular injury. It is unknown whether long-term exposure to ET-1 overexpression results in persistent BP elevation and vascular injury...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27746673/transthyretin-represses-neovascularization-in-diabetic-retinopathy
#13
Jun Shao, Yong Yao
PURPOSE: The apoptosis of human umbilical vein endothelial cells has been reportedly induced by the protein transthyretin (TTR). In human ocular tissue, TTR is generally considered to be secreted mainly by retinal pigment epithelial cells (hRPECs); however, whether TTR affects the development of neovascularization in diabetic retinopathy (DR) remains unclear. METHODS: Natural and simulated DR media were used to culture human retinal microvascular endothelial cells (hRECs)...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27738012/self-renewal-of-a-purified-tie2-hematopoietic-stem-cell-population-relies-on-mitochondrial-clearance
#14
Kyoko Ito, Raphaël Turcotte, Jinhua Cui, Samuel E Zimmerman, Sandra Pinho, Toshihide Mizoguchi, Fumio Arai, Judith M Runnels, Clemens Alt, Julie Teruya-Feldstein, Jessica C Mar, Rajat Singh, Toshio Suda, Charles P Lin, Paul S Frenette, Keisuke Ito
A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. The mechanisms of HSC division balance, however, are not yet defined. Here we demonstrate, by characterizing at the single cell level a purified and minimally heterogeneous Tie2(+) HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality-control process in mitochondria, plays an essential role in self-renewing expansion of Tie2(+) HSCs...
October 13, 2016: Science
https://www.readbyqxmd.com/read/27712004/pulmonary-vascular-inflammation-effect-of-tlr-signaling-on-angiopoietin-tie-regulation
#15
Tobias Hilbert, Kathrin Dornbusch, Georg Baumgarten, Andreas Hoeft, Stilla Frede, Sven Klaschik
Increased pulmonary vascular resistance is a critical complication in sepsis. Toll-like receptor (TLR) as well as angiopoietin (ANG) signaling both contribute to the emergence of pulmonary arterial hypertension. We hypothesized that TLR stimulation by bacterial ligands directly affects expression and secretion of ligands and receptors of the angiopoietin/TIE axis. Microvascular endothelial (HPMEC) and smooth muscle cells (SMC) of pulmonary origin were incubated with thrombin and with ligands for TLR2, -4, -5, and -9...
October 6, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27698866/4-isothiocyanate-2-2-6-6-tetramethyl-piperidinooxyl-inhibits-angiogenesis-by-suppressing-vegfr2-and-tie2-phosphorylation
#16
Yuanyuan Liu, Jing Gao, Shuangsheng Huang, Lamei Hu, Zhiqiang Wang, Zheyuan Wang, Xiao Chen, Xiaoyu Zhang, Wenguang Li
Reactive oxygen species (ROS) are involved in the signaling pathway and are triggered by angiogenic factors, including vascular endothelial growth factor and angiopoietins. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl (4-ISO-Tempo) is one of the nitroxides that exhibits antioxidant activity. However, the anti-angiogenic effect of 4-ISO-Tempo remains unknown. The aim of this study was to investigate the effect of 4-ISO-Tempo on tumor proliferation and angiogenesis as well as its underlying mechanisms...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27695111/constitutive-association-of-tie1-and-tie2-with-endothelial-integrins-is-functionally-modulated-by-angiopoietin-1-and-fibronectin
#17
Annamarie C Dalton, Tomer Shlamkovitch, Niv Papo, William A Barton
Functional cross-talk between Tie2 and Integrin signaling pathways is essential to coordinate endothelial cell adhesion and migration in response to the extracellular matrix, yet the mechanisms behind this phenomenon are unclear. Here, we examine the possibility that receptor cross-talk is driven through uncharacterized Tie-integrin interactions on the endothelial surface. Using a live cell FRET-based proximity assay, we monitor Tie-integrin receptor recognition and demonstrate that both Tie1 and Tie2 readily associate with integrins α5ß1 and αVß3 through their respective ectodomains...
2016: PloS One
https://www.readbyqxmd.com/read/27686285/cthrc1-promotes-angiogenesis-by-recruiting-tie2-expressing-monocytes-to-pancreatic-tumors
#18
Jaemin Lee, Jinhoi Song, Eun-Soo Kwon, Seongyea Jo, Min Kyung Kang, Yeon Jeong Kim, Yeonsil Hwang, Hosung Bae, Tae Heung Kang, Suhwan Chang, Hee Jun Cho, Song Cheol Kim, Seokho Kim, Sang Seok Koh
CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis...
September 30, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27683636/pharmacological-tie2-activation-in-kidney-transplantation
#19
Kristina Thamm, Florence Njau, Paul Van Slyke, Daniel J Dumont, Joon-Keun Park, Hermann Haller, Sascha David
AIM: To investigate the therapeutic potential of vasculotide (VT) - a Tie2 activating therapeutic - in kidney transplantation. METHODS: We performed a murine MHC-mismatched renal transplant model (C57Bl/6 male into Balb/c female) with 60 min cold and 30 min warm ischemia time. 500 ng VT was administered i.p. to donor mice 1 h before organ removal. In addition, recipients received 500 ng VT i.p. directly and 3 d after surgery. Survival was monitored and remaining animals were sacrificed 28 d after transplantation...
September 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/27682210/differential-expression-of-systemic-inflammatory-mediators-in-amputees-with-chronic-residual-limb-pain
#20
Alexander Chamessian, Thomas Van de Ven, Thomas Buchheit, Hung-Lun Hsia, Mary McDuffie, Eric R Gamazon, Colin Walsh, Stephen Bruehl, Chester 'Trip' Buckenmaier, Andrew Shaw
Chronic post-surgical pain impacts the majority of amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute post-amputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research (VIPER) study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Subjects included 36 recent active duty military traumatic amputees with chronic residual limb pain and 40 without clinically significant pain...
September 23, 2016: Pain
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