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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
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
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
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
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
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
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
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
Giselle A Suero-Abreu, Orlando Aristizábal, Benjamin B Bartelle, Eugenia Volkova, Joe J Rodríguez, Daniel H Turnbull
PURPOSE: In this study, we evaluated a genetic approach for in vivo multimodal molecular imaging of vasculature in a mouse model of melanoma. PROCEDURES: We used a novel transgenic mouse, Ts-Biotag, that genetically biotinylates vascular endothelial cells. After inoculating these mice with B16 melanoma cells, we selectively targeted endothelial cells with (strept)avidinated contrast agents to achieve multimodal contrast enhancement of Tie2-expressing blood vessels during tumor progression...
September 27, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
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
Avinash V Dharmadhikari, Jenny J Sun, Krzysztof Gogolewski, Brandi L Carofino, Vladimir Ustiyan, Misty Hill, Tadeusz Majewski, Przemyslaw Szafranski, Monica J Justice, Russell S Ray, Mary E Dickinson, Vladimir V Kalinichenko, Anna Gambin, Pawel Stankiewicz
FOXF1 heterozygous point mutations and genomic deletions have been reported in newborns with a neonatally lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). However, no gain-of-function mutations in FOXF1 have been identified yet in human disease. To study the effects of FOXF1 overexpression in lung development, we generated a Foxf1 overexpression mouse model by knocking in a Cre-inducible Foxf1 allele into the ROSA26 (R26) locus. The mice were phenotyped using micro-computed tomography (micro-CT), head-out plethysmography, ChIP-seq and transcriptome analyses, immunohistochemistry, and lung histopathology...
September 16, 2016: Biology Open
Elizabeth Dumas, Paul-Eduard Neagoe, Patrick P McDonald, Michel White, Martin G Sirois
We reported the expression of angiopoietin Tie2 receptor on human neutrophils and the capacity of angiopoietins (Ang1 and Ang2) to induce pro-inflammatory activities, such as platelet-activating factor synthesis, β2-integrin activation and neutrophil migration. Recently, we observed differential effects between both angiopoietins, namely, the capacity of Ang1, but not Ang2, to promote rapid interleukin-8 synthesis and release, as well as neutrophil viability. Herein, we addressed whether Ang1 and/or Ang2 could modulate the synthesis and release of macrophage inflammatory protein-1β (MIP-1β) by neutrophils...
2016: PloS One
Vishal R Yadav, Ka L Hong, Darryl C Zeldin, Mohammed A Nayeem
Soluble epoxide hydrolase (sEH) converts epoxyeicosatrienoic acids that are endothelium-derived hyperpolarizing factors into less active dihydroxyeicosatrienoic acids. Previously, we reported a decrease in adenosine A1 receptor (A1AR) protein levels in sEH knockout (sEH(-/-)) and an increase in sEH and A1AR protein levels in A2AAR(-/-) mice. Additionally, KATP channels are involved in adenosine receptor (AR)-dependent vascular relaxation. Thus, we hypothesize that a potential relationship may exist among sEH over-expression, A1AR upregulation, inactivation of KATP channels, and increased in vascular tone...
November 2016: Molecular and Cellular Biochemistry
Shailesh Agarwal, Shawn Loder, David Cholok, Joshua Peterson, John Li, David Fireman, Christopher Breuler, Hsiao Sung Hsieh, Kavitha Ranganathan, Charles Hwang, James Drake, Shuli Li, Charles K Chan, Michael T Longaker, Benjamin Levi
Endothelial-to-mesenchymal transition (EndMT) has been implicated in a variety of aberrant wound healing conditions. However, unambiguous evidence of EndMT has been elusive due to limitations of in vitro experimental designs and animal models. In vitro experiments cannot account for the myriad ligands and cells which regulate differentiation, and in vivo tissue injury models may induce lineage-independent endothelial marker expression in mesenchymal cells. By using an inducible Cre model to mark mesenchymal cells (Scx-creERT/tdTomato + ) prior to injury, we demonstrate that musculoskeletal injury induces expression of CD31, VeCadherin, or Tie2 in mesenchymal cells...
2016: Scientific Reports
Govinda Bhattarai, Sung-Ho Kook, Jae-Hwan Kim, Sher Bahadur Poudel, Shin-Saeng Lim, Young-Kwon Seo, Jeong-Chae Lee
COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent enhancing tissue regeneration with increased angiogenesis. However, the effect of COMP-Ang1 on periodontitic tissue damages and the related mechanisms are not yet investigated. We initially explored whether a local delivery of COMP-Ang1 protects lipopolysaccharide (LPS)/ligature-induced periodontal destruction in rats. As the results, μCT and histological analyses revealed that COMP-Ang1 inhibits LPS-mediated degradation of periodontium...
November 2016: Bone
Berta Almoguera, Lyam Vazquez, Frank Mentch, John Connolly, Jennifer A Pacheco, Agnes S Sundaresan, Peggy L Peissig, James G Linneman, Catherine A McCarty, David Crosslin, David S Carrell, Todd Lingren, Bahram Namjou-Khales, John B Harley, Eric Larson, Gail P Jarvik, Murray Brilliant, Marc S Williams, Iftikhar J Kullo, Erik B Hysinger, Patrick M A Sleiman, Hakon Hakonarson
RATIONALE: Despite significant advances in our knowledge of the genetic architecture of asthma, specific contributors to the variability in the burden between populations remain uncovered. OBJECTIVE: To identify additional genetic susceptibility factors of asthma in European American and African American populations. METHODS: A phenotyping algorithm mining Electronic Medical Records was developed and validated to recruit cases with asthma and controls from the eMERGE (electronic Medical Records and Genomics) network...
September 9, 2016: American Journal of Respiratory and Critical Care Medicine
Stefania Fiorcari, Rossana Maffei, Valentina Audrito, Silvia Martinelli, Elisa Ten Hacken, Patrizia Zucchini, Giulia Grisendi, Leonardo Potenza, Mario Luppi, Jan A Burger, Silvia Deaglio, Roberto Marasca
In lymphoid organs, nurse-like cells (NLCs) show properties of tumor-associated macrophages, playing a crucial role in chronic lymphocytic leukemia (CLL) cell survival. Ibrutinib, a potent inhibitor of Bruton's tyrosine kinase (BTK), is able to counteract pro-survival signals in CLL cells. Since the effects on CLL cells have been studied in the last years, less is known about the influence of ibrutinib on NLCs properties. We sought to determine how ibrutinib modifies NLCs functions focusing on the balance between immunosuppressive and inflammatory features...
September 1, 2016: Oncotarget
Zi-Xue Xuan, Su Zhang, Shou-Jun Yuan, Wei Wang, Jia Yu
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer deaths worldwide. The targeted therapy had made important progress in recent years, but few potential predictive biomarkers for prognosis of NSCLC patients were identified. Angiopoietin-2 (Ang-2), a cytokine upregulated in tumor endothelial cells and some tumor cells including NSCLC, is a partial agonist and antagonist of angiopoietin-1 (Ang-1). Ang-1 is another ligand for the tyrosine kinase receptor Tie2; it promotes recruitment of pericytes and smooth muscle cells, stabilizing vascular networks by binding to Tie2...
2016: World Journal of Surgical Oncology
Hao Wang, Cheng Hang, Xi-Long Ou, Jin-Shan Nie, Yi-Tao Ding, Shi-Gui Xue, Hua Gao, Jian-Xin Zhu
BACKGROUND: Pancreatic cancer is currently one of the leading causes of cancer deaths without any effective therapies. Mir-145 has been found to be tumor-suppressive in various types of cancers. The aim of this study is to investigate the role of miR-145 in pancreatic cancer cells and explore its underlying mechanism. METHODS: Quantitative real time PCR was used to determine the expression level of miR-145 and angiopoietin-2 (Ang-2) mNRA, and the expression level of Ang-2 protein was measured by western blotting...
2016: Cancer Cell International
S R Mishra, M S Parmar, V P Yadav, R Reshma, J Bharati, M K Bharti, A Paul, V S Chouhan, G Taru Sharma, G Singh, M Sarkar
The objective of this study was to document the expression and localization of angiopoietin (ANGPT) family members comprising of angiopoietin (ANGPT1 and ANGPT2), and their receptors (Tie1 and Tie2) in buffalo corpus luteum (CL) obtained from different stages of the oestrous cycle, and the modulatory role of ANGPT1 and ANGPT2 alone or in combinations on progesterone (P4 ) secretion and mRNA expression of phosphotidylinositide-3kinase-protein kinase B (PI3K-AKT), phosphoinositide-dependent kinase (PDK), protein kinase B (AKT), Bcl2 associated death promoter (BAD), caspase 3 and von willebrand factor (vWF) in luteal cells obtained from midluteal phase (MLP) of oestrous cycle in buffalo...
August 28, 2016: Reproduction in Domestic Animals, Zuchthygiene
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