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https://www.readbyqxmd.com/read/29323190/angiopoietins-bind-thrombomodulin-and-inhibit-its-function-as-a-thrombin-cofactor
#1
Christopher Daly, Xiaozhong Qian, Carla Castanaro, Elizabeth Pasnikowski, Xiabo Jiang, Benjamin R Thomson, Susan E Quaggin, Nicholas Papadopoulos, Yang Wei, John S Rudge, Gavin Thurston, George D Yancopoulos, Samuel Davis
Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) are ligands for Tie2, an endothelial-specific receptor tyrosine kinase that is an essential regulator of angiogenesis. Here we report the identification, via expression cloning, of thrombomodulin (TM) as another receptor for Ang1 and Ang2. Thrombomodulin is an endothelial cell surface molecule that plays an essential role as a coagulation inhibitor via its function as a cofactor in the thrombin-mediated activation of protein C, an anticoagulant protein, as well as thrombin-activatable fibrinolysis inhibitor (TAFI)...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318723/endothelium-specific-cyp2j2-overexpression-attenuates-age-related-insulin-resistance
#2
Yan Yang, Ruolan Dong, Zhihui Chen, Danli Hu, Menglu Fu, Ying Tang, Dao Wen Wang, Xizhen Xu, Ling Tu
Ample evidences demonstrate that cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, and cardiovascular protective effects. In this study, we investigated the effects of endothelium-specific CYP2J2 overexpression on age-related insulin resistance and metabolic dysfunction. Endothelium-specific targeting of the human CYP epoxygenase, CYP2J2, transgenic mice (Tie2-CYP2J2-Tr mice) was utilized. The effects of endothelium-specific CYP2J2 overexpression on aging-associated obesity, inflammation, and peripheral insulin resistance were evaluated by assessing metabolic parameters in young (3 months old) and aged (16 months old) adult male Tie2-CYP2J2-Tr mice...
January 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29304157/conditional-deletion-of-rb1-in-the-tie2-lineage-leads-to-aortic-valve-regurgitation
#3
Marina Freytsis, Lauren Baugh, Zhiyi Liu, Irene Georgakoudi, Philip W Hinds, Lauren D Black, Gordon S Huggins
OBJECTIVE: Aortic valve disease is a complex process characterized by valve interstitial cell activation, disruption of the extracellular matrix culminating in valve mineralization occurring over many years. We explored the function of the retinoblastoma protein (pRb) in aortic valve disease, given its critical role in mesenchymal cell differentiation including bone development and mineralization. APPROACH AND RESULTS: We generated a mouse model of conditional pRb knockout (cKO) in the aortic valve regulated by Tie2-Cre-mediated excision of floxed RB1 alleles...
2018: PloS One
https://www.readbyqxmd.com/read/29295986/macrophages-orchestrate-breast-cancer-early-dissemination-and-metastasis
#4
Nina Linde, Maria Casanova-Acebes, Maria Soledad Sosa, Arthur Mortha, Adeeb Rahman, Eduardo Farias, Kathryn Harper, Ethan Tardio, Ivan Reyes Torres, Joan Jones, John Condeelis, Miriam Merad, Julio A Aguirre-Ghiso
Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2+ breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206+/Tie2+ macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2+ early cancer cells...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29291395/erbb2-promotes-endothelial-phenotype-of-human-left-ventricular-epicardial-highly-proliferative-cells-ehipc
#5
Sergey Ryzhov, Michael P Robich, Daniel J Roberts, Amanda J Favreau-Lessard, Sarah M Peterson, Edward Jachimowicz, Rutwik Rath, Calvin P H Vary, Reed Quinn, Robert S Kramer, Douglas B Sawyer
The adult human heart contains a subpopulation of highly proliferative cells. The role of ErbB receptors in these cells has not been studied. From human left ventricular (LV) epicardial biopsies, we isolated highly proliferative cells (eHiPC) to characterize the cell surface expression and function of ErbB receptors in the regulation of cell proliferation and phenotype. We found that human LV eHiPC express all four ErbB receptor subtypes. However, the expression of ErbB receptors varied widely among eHiPC isolated from different subjects...
December 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29259905/negative-effects-of-transthyretin-in-high-myopic-vitreous-on-diabetic-retinopathy
#6
Jun Shao, Yong Yao
AIM: To analyze the relationship between vitreous transthyretin (TTR) levels, high myopia and diabetic retinopathy (DR). METHODS: We selected 6722 individuals from the southern Jiangsu Province for diabetes and ophthalmic examinations. The TTR concentration in the vitreous of 50 patients with high myopia and diabetes, 50 patients with only DR, and 20 healthy controls were determined by ELISA. Key factors in Tie2 pathway in DR development including vascular endothecial growth factor (VEGF), Tie2, Angpt1, Angpt2, vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 were also detected by ELISA...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29246296/antisense-oligonucleotides-targeting-y-box-binding-protein-1-inhibit-tumor-angiogenesis-by-downregulating-bcl-xl-vegfr2-tie-axes
#7
Kiyoko Setoguchi, Lin Cui, Nobutaka Hachisuka, Sumalee Obchoei, Kentaro Shinkai, Fuminori Hyodo, Kiyoko Kato, Fumito Wada, Tsuyoshi Yamamoto, Mariko Harada-Shiba, Satoshi Obika, Kenji Nakano
Y-box binding protein-1 (YB-1), involved in cancer progression and chemoradiation resistance, is overexpressed in not only cancer cells but also tumor blood vessels. In this study, we investigated the potential value of amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides (ASOs) targeting YB-1 (YB-1 ASOA) as an antiangiogenic cancer therapy. YB-1 ASOA was superior to natural DNA-based ASO or locked nucleic acid (LNA)-modified YB-1 ASO in both knockdown efficiency and safety, the latter assessed by liver function...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29237738/ascending-vasa-recta-are-angiopoietin-tie2-dependent-lymphatic-like-vessels
#8
Yael Kenig-Kozlovsky, Rizaldy P Scott, Tuncer Onay, Isabel Anna Carota, Benjamin R Thomson, Hyea Jin Gil, Veronica Ramirez, Shinji Yamaguchi, Christine E Tanna, Stefan Heinen, Christine Wu, Radu V Stan, Janet D Klein, Jeff M Sands, Guillermo Oliver, Susan E Quaggin
Urinary concentrating ability is central to mammalian water balance and depends on a medullary osmotic gradient generated by a countercurrent multiplication mechanism. Medullary hyperosmolarity is protected from washout by countercurrent exchange and efficient removal of interstitial fluid resorbed from the loop of Henle and collecting ducts. In most tissues, lymphatic vessels drain excess interstitial fluid back to the venous circulation. However, the renal medulla is devoid of classic lymphatics. Studies have suggested that the fenestrated ascending vasa recta (AVRs) drain the interstitial fluid in this location, but this function has not been conclusively shown...
December 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29219024/excess-maternal-thyroxine-alters-the-proliferative-activity-and-angiogenic-profile-of-growth-cartilage-of-rats-at-birth-and-weaning
#9
Lorena Gabriela Rocha Ribeiro, Juneo Freitas Silva, Natália de Melo Ocarino, Cíntia Almeida de Souza, Eliane Gonçalves de Melo, Rogéria Serakides
Objective The aim of this study was to unravel the mechanisms by which thyroxine affects skeletal growth by evaluating proliferative activity and angiogenic profile of growth cartilage of neonatal and weanling rats. Methods Sixteen adult Wistar rats were equally divided into 2 groups: control and treated with thyroxine during pregnancy and lactation. The weight, measurement of plasma free T4 and thyroids, femurs' histomorphometric analysis, and proliferative activity and angiogenic profile by immunohistochemical or real-time reverse transcriptase-polymerase chain reaction in growth cartilage was performed...
January 2018: Cartilage
https://www.readbyqxmd.com/read/29217526/first-in-human-phase-i-study-of-single-agent-vanucizumab-a-first-in-class-bi-specific-anti-ang-2-anti-vegf-antibody-in-adult-patients-with-advanced-solid-tumors
#10
Manuel Hidalgo, Maria Martinez-Garcia, Christophe Le Tourneau, Christophe Massard, Elena Garralda, Valentina Boni, Alvaro Taus, Joan Albanell, Marie-Paule Sablin, Marie Alt, Rastilav Bahleda, Andreea Varga, Christophe Boetsch, Izolda Franjkovic, Florian Heil, Angelika Lahr, Katharina Lechner, Anthony Morel, Tapan K Nayak, Simona Rossomanno, Kevin Smart, Kay-Gunnar Stubenrauch, Oliver Krieter
PURPOSE: Vanucizumab is an investigational anti-angiogenic, first-in-class, bi-specific monoclonal antibody targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard therapies. EXPERIMENTAL DESIGN: Patients received escalating bi-weekly (q2w; 3-30 mg/kg) or weekly (qw; 10-30 mg/kg) intravenous doses guided by a Bayesian logistic regression model with overdose control...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29212268/comp-angiopoietin-1-mitigates-changes-in-lipid-droplet-size-macrophage-infiltration-of-adipose-tissue-and-renal-inflammation-in-streptozotocin-induced-diabetic-mice
#11
Yu Jin Jung, Woong Park, Tung Nguyen-Thanh, Kyung Pyo Kang, Heung Young Jin, Suhn Hee Kim, Wonhee Suh, Won Kim
Adipose tissue is considered to be an endocrine organ, and adipocyte size correlates with insulin resistance and metabolic parameters in obesity. There is little data on the effects of angiopoietin-1 in adipose tissue and kidney in streptozotocin (STZ)-induced diabetes. In this study, we investigated the protective effect of COMP-angiopoietin-1 (COMP-Ang1), a potent variant of angiopoietin-1, on vascular endothelial cells in epididymal adipose tissue and its regulatory effect on other metabolic parameters, such as lipid droplet diameter, macrophage infiltration, and renal inflammation in STZ-treated mice...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29191922/adventitial-sca1-stem-cell-antigen-1-cells-transduced-with-etv2-ets-variant-2-are-committed-to-the-endothelial-fate-and-improve-vascular-remodeling-after-injury
#12
Alexandra Le Bras, Baoqi Yu, Shirin Issa Bhaloo, Xuechong Hong, Zhongyi Zhang, Yanhua Hu, Qingbo Xu
OBJECTIVE: Vascular adventitial Sca1+ (stem cell antigen-1) progenitor cells preferentially differentiate into smooth muscle cells, which contribute to vascular remodeling and neointima formation in vessel grafts. Therefore, directing the differentiation of Sca1+ cells toward the endothelial lineage could represent a new therapeutic strategy against vascular disease. APPROACH AND RESULTS: We thus developed a fast, reproducible protocol based on the single-gene transfer of ETV2 (ETS variant 2) to differentiate Sca1+ cells toward the endothelial fate and studied the effect of cell conversion on vascular hyperplasia in a model of endothelial injury...
November 30, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29190766/developmental-peculiarities-in-placentae-of-ovine-uniparental-conceptuses
#13
Roberta Arena, Federica Zacchini, Paola Toschi, Luca Palazzese, Marta Czernik, Grażyna Ewa Ptak
Genomic imprinting is an epigenetic phenomenon regulating mono-allelic expression of genes depending on their parental origin. Defective genomic imprinting is involved in several placental disorders, such as intrauterine growth restriction and pre-eclampsia. Uniparental embryos, having maternal-only or paternal-only genomes (parthenogenotes [PAR] and androgenotes [AND], respectively), are useful models to study placentation. The aim of this work was to reveal the effect of parental genome (maternal and paternal) on placentation...
2017: PloS One
https://www.readbyqxmd.com/read/29180303/effects-of-erythropoietin-on-astrocytes-and-brain-endothelial-cells-in-primary-culture-during-anoxia-depend-on-simultaneous-signaling-by-other-cytokines-and-on-duration-of-anoxia
#14
Hameed Al-Sarraf, Slava Malatiali, Mariam Al-Awadi, Zoran Redzic
Studies on animals revealed neuroprotective effects of exogenously applied erythropoietin (EPO) during cerebral ischemia/hypoxia. Yet, application of exogenous EPO in stroke patients often lead to haemorrhagic transformation. To clarify potential mechanism of this adverse effect we explored effects of EPO on viabilities of astrocytes and brain endothelial cells (BECs) in primary culture during anoxia of various durations, in the presence or absence of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), which are cytokines that are also released from the neurovascular unit during hypoxia...
November 24, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29154961/inhibition-of-cyclooxygenase-cox-2-suppresses-the-recruitment-of-endothelial-progenitor-cells-in-the-microvasculature-of-endometriotic-lesions
#15
Jeannette Rudzitis-Auth, Ruth M Nickels, Michael D Menger, Matthias W Laschke
The incorporation of endothelial progenitor cells (EPCs) into newly developing blood vessels contributes to the vascularization of endometriotic lesions. here, we analyzed whether cyclooxygenase (COX)-2 signaling regulates this vasculogenic process. Endometriotic lesions were surgically induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein (GFP)) 287 Sato mice. The animals received β-estradiol 17-valerate once a week and were daily treated with the selective COX-2 inhibitor parecoxib (25 mg/kg) or vehicle (control) over 7 and 28 days...
November 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29149941/pathophysiology-of-septic-shock
#16
REVIEW
James A Russell, Barret Rush, John Boyd
Fundamental features of septic shock are vasodilation, increased permeability, hypovolemia, and ventricular dysfunction. Vasodilation owing to increased nitric oxide and prostaglandins is treated with vasopressors (norepinephrine first). Increased permeability relates to several pathways (Slit/Robo4, vascular endothelial growth factor, angiopoietin 1 and 2/Tie2 pathway, sphingosine-1-phosphate, and heparin-binding protein), some of which are targets for therapies. Hypovolemia is common and crystalloid is recommended for fluid resuscitation...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29132435/vasculotide-reduces-pulmonary-hyperpermeability-in-experimental-pneumococcal-pneumonia
#17
Birgitt Gutbier, Xiaohui Jiang, Kristina Dietert, Carolin Ehrler, Jasmin Lienau, Paul Van Slyke, Harold Kim, Van C Hoang, Jason T Maynes, Daniel J Dumont, Achim D Gruber, Norbert Weissmann, Timothy J Mitchell, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality worldwide. Despite effective antimicrobial therapy, CAP can induce pulmonary endothelial hyperpermeability resulting in life-threatening lung failure due to an exaggerated host-pathogen interaction. Treatment of acute lung injury is mainly supportive because key elements of inflammation-induced barrier disruption remain undetermined. Angiopoietin-1 (Ang-1)-mediated Tie2 activation reduces, and the Ang-1 antagonist Ang-2 increases, inflammation and endothelial permeability in sepsis...
November 13, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29125991/effects-of-quercetin-combined-with-anticancer-drugs-on-metastasis-associated-factors-of-gastric-cancer-cells-in-vitro-and-in-vivo-studies
#18
Cing-Syuan Lei, Yu-Chen Hou, Man-Hui Pai, Ming-Tsan Lin, Sung-Ling Yeh
Chemotherapy is essential to most patients with gastric cancer and the anticancer drug, irinotecan (CPT-11), and its metabolite, SN-38, an inhibitor of DNA topoisomerase I, are first-line chemotherapies for gastric cancer. Quercetin, a flavonoid that is widely found in various vegetables and fruits, has the ability to potentiate the efficacy of anticancer drugs. The purpose of this study was to investigate the therapeutic effect of quercetin combined with irinotecan/SN-38 in the AGS human gastric cancer cell line in vitro and in vivo...
September 28, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29115538/complementary-actions-of-melatonin-on-angiogenic-factors-the-angiopoietin-tie2-axis-and-vegf-in-co%C3%A2-cultures-of-human-endothelial-and-breast-cancer-cells
#19
Alicia González-González, Alicia González, Carolina Alonso-González, Javier Menéndez-Menéndez, Carlos Martínez-Campa, Samuel Cos
Melatonin exerts oncostatic activity in breast cancer through antiangiogenic actions. There, the aim of the present study was to ascertain whether melatonin modulates, in a coordinated action, angiopoietin-1 (ANG-1), ANG-2, their cognate Tie2 receptor and VEGF in co-cultures of human endothelial cells (HUVECs) and breast cancer (MCF-7) cells. To accomplish this we used co-cultures of human breast cancer cells (MCF-7) or non-malignant human mammary epithelial cells (MCF‑10A) with endothelial cells (HUVECs)...
November 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29101349/t-cells-upon-activation-promote-endothelin-1-production-in-monocytes-via-ifn-%C3%AE-and-tnf-%C3%AE
#20
Shoshi Shinagawa, Takahiro Okazaki, Mari Ikeda, Kazuo Yudoh, Yaz Y Kisanuki, Masashi Yanagisawa, Kimito Kawahata, Shoichi Ozaki
Endothelin 1 (ET-1), mainly produced from vascular endothelial cells, induces vasoconstriction in physiological conditions. The endothelin receptor antagonist is among the most effective agents for pulmonary hypertension. However, little is known about the production source of ET-1 in inflammation and immunity. Here, we studied whether T cell-mediated ET-1 production system exists and operates independent of the production system in vascular endothelial cells. ET-1 production was readily detectable in the culture supernatant of human PBMCs and murine spleen cells stimulated with anti-CD3 antibody...
November 3, 2017: Scientific Reports
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