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https://www.readbyqxmd.com/read/27916465/hypoxia-inhibits-lymphatic-thoracic-duct-formation-in-zebrafish
#1
Isabelle Ernens, Andrew I Lumley, Lu Zhang, Yvan Devaux, Daniel R Wagner
Hypoxia promotes blood vessel growth through up-regulation of pro-angiogenic pathways but its role on the lymphatic system remains unclear. The homeobox transcription factor Prox1 is a master control gene for generating lymphatic endothelial cells (LECs) and is up-regulated by hypoxia-inducible factors in mammals. While vascular endothelial growth factor A (VEGFA) is critical for angiogenesis, VEGFC and its receptor VEGF receptor-3 (VEGFR-3) are essential for the initial sprouting and directed migration as well as for the subsequent survival of LECs...
December 1, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913637/mural-endothelial-cell-cell-interactions-stabilize-the-developing-zebrafish-dorsal-aorta
#2
Amber N Stratman, Sofia A Pezoa, Olivia M Farrelly, Daniel Castranova, Louis E Dye, Matthew G Butler, Harwin Sidik, William S Talbot, Brant M Weinstein
Mural cells (vascular smooth muscle cells and pericytes) play a critical role in the development of the vasculature, promoting vascular quiescence and long-term vessel stabilization through their interactions with endothelial cells. However, the mechanistic details of how mural cells stabilize vessels are not fully understood. We have examined the emergence and functional role of mural cells investing the dorsal aorta during early development using the zebrafish. Consistent with previous literature, our data suggest that cells ensheathing the dorsal aorta emerge from a sub-population of cells in the adjacent sclerotome...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27892483/down-regulation-of-coasy-the-gene-associated-with-nbia-vi-reduces-bmp-signaling-perturbs-dorso-ventral-patterning-and-alters-neuronal-development-in-zebrafish
#3
Deepak Khatri, Daniela Zizioli, Natascia Tiso, Nicola Facchinello, Sara Vezzoli, Alessandra Gianoncelli, Maurizio Memo, Eugenio Monti, Giuseppe Borsani, Dario Finazzi
Mutations in Pantothenate kinase 2 and Coenzyme A (CoA) synthase (COASY), genes involved in CoA biosynthesis, are associated with rare neurodegenerative disorders with brain iron accumulation. We showed that zebrafish pank2 gene plays an essential role in brain and vasculature development. Now we extended our study to coasy. The gene has high level of sequence identity with the human ortholog and is ubiquitously expressed from the earliest stages of development. The abrogation of its expression led to strong reduction of CoA content, high lethality and a phenotype resembling to that of dorsalized mutants...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882487/delivery-of-small-interfering-rna-to-inhibit-vascular-endothelial-growth-factor-in-zebrafish-using-natural-brain-endothelia-cell-secreted-exosome-nanovesicles-for-the-treatment-of-brain-cancer
#4
Tianzhi Yang, Brittany Fogarty, Bret LaForge, Salma Aziz, Thuy Pham, Leanne Lai, Shuhua Bai
Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0...
November 23, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27877088/aloe-emodin-suppresses-hypoxia-induced-retinal-angiogenesis-via-inhibition-of-hif-1%C3%AE-vegf-pathway
#5
Jianming Wu, Xiao Ke, Wei Wang, Hongcheng Zhang, Na Ma, Wei Fu, Manxi Zhao, Xiaoping Gao, Xiaofeng Hao, Zhirong Zhang
Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. Methods: We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl2 to the ARPE-19 cells, then treated the cells with different concentrations of AE (0...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27876801/ppfia1-drives-active-%C3%AE-5%C3%AE-1-integrin-recycling-and-controls-fibronectin-fibrillogenesis-and-vascular-morphogenesis
#6
Giulia Mana, Fabiana Clapero, Emiliano Panieri, Valentina Panero, Ralph T Böttcher, Hui-Yuan Tseng, Federico Saltarin, Elena Astanina, Katarzyna I Wolanska, Mark R Morgan, Martin J Humphries, Massimo M Santoro, Guido Serini, Donatella Valdembri
Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives endothelial cell (EC) polarity and vascular remodelling. However, mechanisms coordinating α5β1 integrin-mediated extracellular FN endocytosis and exocytosis of newly synthesized FN remain elusive. Here we show that, on Rab21-elicited internalization, FN-bound/active α5β1 is recycled to the EC surface. We identify a pathway, comprising the regulators of post-Golgi carrier formation PI4KB and AP-1A, the small GTPase Rab11B, the surface tyrosine phosphatase receptor PTPRF and its adaptor PPFIA1, which we propose acts as a funnel combining FN secretion and recycling of active α5β1 integrin from the trans-Golgi network (TGN) to the EC surface, thus allowing FN fibrillogenesis...
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27858360/transgenic-zebrafish
#7
Xiaowen Chen, Dafne Gays, Massimo M Santoro
The generation and use of transgenic animals carrying exogenous pieces of DNA stably integrated in their genome is a quite common practice in modern laboratories. Zebrafish have been increasingly used for transgenesis studies mainly due to easy egg accessibility and manipulation together with relatively short generation time. The zebrafish transgenic technology becomes very useful when coupled to continuous in vivo observation of the vertebrate embryonic vasculature. Here we describe the most common technique to generate zebrafish transgenic fish using the Tol2-based methodology and their applications to visualize vascular tissues or endothelial cells in vivo and for functional tumor angiogenesis studies...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27852438/radial-glia-regulate-vascular-patterning-around-the-developing-spinal-cord
#8
Ryota L Matsuoka, Michele Marass, Avdesh Avdesh, Christian Sm Helker, Hans-Martin Maischein, Ann S Grosse, Harmandeep Kaur, Nathan D Lawson, Wiebke Herzog, Didier Yr Stainier
Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial glia ablation in zebrafish embryos leads to excessive sprouting of the trunk vessels around the spinal cord, and exclusively those of venous identity. Mechanistically, we determined that radial glia control this process via the Vegf decoy receptor sFlt1: sflt1 mutants exhibit the venous over-sprouting observed in radial glia-ablated larvae, and sFlt1 overexpression rescues it...
November 17, 2016: ELife
https://www.readbyqxmd.com/read/27835862/a-novel-mutation-in-nuclear-prelamin-a-recognition-factor-like-causes-diffuse-pulmonary-arteriovenous-malformations
#9
Hong-Zhou Liu, Chun-Xian Du, Jing Luo, Xue-Ping Qiu, Zu-Hua Li, Qi-Yong Lou, Zhan Yin, Fang Zheng
Two daughters in a Chinese consanguineous family were diagnosed as diffuse pulmonary arteriovenous malformations (PAVMs) and screened using whole exome sequencing (WES) and copy number variations (CNVs) chips. Though no mutation was found in the established causative genes of capillary malformation-AVMs (CM-AVMs) or PAVMs, Ser161Ile (hg19 NM_022493 c.482G>T) mutation in nuclear prelamin A recognition factor-like (NARFL) was identified. Ser161Ile mutation in NARFL conservation region was predicted to be deleterious and absent in 500 population controls and Exome Aggregation Consortium (ExAC) Database...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834691/zebrafish-model-for-functional-screening-of-flow-responsive-genes
#10
Jovana Serbanovic-Canic, Amalia de Luca, Christina Warboys, Pedro F Ferreira, Le A Luong, Sarah Hsiao, Ismael Gauci, Marwa Mahmoud, Shuang Feng, Celine Souilhol, Neil Bowden, John-Paul Ashton, Henning Walczak, David Firmin, Rob Krams, Justin C Mason, Dorian O Haskard, Spencer Sherwin, Victoria Ridger, Timothy J A Chico, Paul C Evans
OBJECTIVE: Atherosclerosis is initiated at branches and bends of arteries exposed to disturbed blood flow that generates low shear stress. This mechanical environment promotes lesions by inducing endothelial cell (EC) apoptosis and dysfunction via mechanisms that are incompletely understood. Although transcriptome-based studies have identified multiple shear-responsive genes, most of them have an unknown function. To address this, we investigated whether zebrafish embryos can be used for functional screening of mechanosensitive genes that regulate EC apoptosis in mammalian arteries...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27809680/in-vivo-functional-consequences-of-human-thra-variants-expressed-in-the-zebrafish
#11
Federica Marelli, Silvia Carra, Giuditta Rurale, Franco Cotelli, Luca Persani
Heterozygous mutations in the thyroid hormone receptor alpha (THRA) gene cause Resistance to Thyroid Hormone alpha (RTHα), a disease characterized by variable manifestations reminiscent of untreated congenital hypothyroidism but a raised T3/T4 ratio and normal TSH levels. We recently described that zebrafish embryos expressing a dominant negative (DN) form of thraa recapitulate the key features of RTHα, and that zebrafish and human receptors are functionally interchangeable. In this study we expressed several human TRα variants in zebrafish embryos and analyzed the resulting phenotypes...
November 3, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27802214/endothelial-cell-dynamics-in-vascular-remodelling
#12
Pedro Barbacena, Joana R Carvalho, Claudio A Franco
In this ESCHM 2016 conference talk report, we summarise two recently published original articles Franco et al. PLoS Biology 2015 and Franco et al. eLIFE 2016. The vascular network undergoes extensive vessel remodelling to become fully functional. Is it well established that blood flow is a main driver for vascular remodelling. It has also been proposed that vessel pruning is a central process within physiological vessel remodelling. However, despite its central function, the cellular and molecular mechanisms regulating vessel regression, and their interaction with blood flow patterns, remain largely unexplained...
October 14, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27792790/phactr1-is-a-genetic-susceptibility-locus-for-fibromuscular-dysplasia-supporting-its-complex-genetic-pattern-of-inheritance
#13
Soto Romuald Kiando, Nathan R Tucker, Luis-Jaime Castro-Vega, Alexander Katz, Valentina D'Escamard, Cyrielle Tréard, Daniel Fraher, Juliette Albuisson, Daniella Kadian-Dodov, Zi Ye, Erin Austin, Min-Lee Yang, Kristina Hunker, Cristina Barlassina, Daniele Cusi, Pilar Galan, Jean-Philippe Empana, Xavier Jouven, Anne-Paule Gimenez-Roqueplo, Patrick Bruneval, Esther Soo Hyun Kim, Jeffrey W Olin, Heather L Gornik, Michel Azizi, Pierre-François Plouin, Patrick T Ellinor, Iftikhar J Kullo, David J Milan, Santhi K Ganesh, Pierre Boutouyrie, Jason C Kovacic, Xavier Jeunemaitre, Nabila Bouatia-Naji
Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P<10-4) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1)...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27792641/lim-domain-only-2-regulates-endothelial-proliferation-angiogenesis-and-tissue-regeneration
#14
Shu Meng, Gianfranco Matrone, Jie Lv, Kaifu Chen, Wing Tak Wong, John P Cooke
BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss- and gain-of-function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. LMO2 KD significantly impaired endothelial proliferation...
October 6, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27792175/the-relationship-between-estrogen-and-nitric-oxide-in-the-prevention-of-cardiac-and-vascular-anomalies-in-the-developing-zebrafish-danio-rerio
#15
Benjamin G Sykes, Peter M Van Steyn, Jonathan D Vignali, John Winalski, Julie Lozier, Wade E Bell, James E Turner
It has been known that both estrogen (E2) and nitric oxide (NO) are critical for proper cardiovascular system (CVS) function. It has also been demonstrated that E2 acts as an upstream effector in the nitric oxide (NO) pathway. Results from this study indicate that the use of a nitric oxide synthase (NOS) inhibitor (NOSI) which targets specifically neuronal NOS (nNOS or NOS1), proadifen hydrochloride, caused a significant depression of fish heart rates (HR) accompanied by increased arrhythmic behavior. However, none of these phenotypes were evident with either the inhibition of endothelial NOS (eNOS) or inducible NOS (iNOS) isoforms...
October 26, 2016: Brain Sciences
https://www.readbyqxmd.com/read/27789478/microrna-126a-directs-lymphangiogenesis-through-interacting-with-chemokine-and-flt4-signaling-in-zebrafish
#16
Jian Chen, Rong-Fang Zhu, Fang-Fang Li, Yu-Lai Liang, Chen Wang, Yong-Wen Qin, Shuang Huang, Xian-Xian Zhao, Qing Jing
OBJECTIVE: MicroRNA-126 (miR-126) is an endothelium-enriched miRNA and functions in vascular integrity and angiogenesis. The application of miRNA as potential biomarker and therapy target has been widely investigated in various pathological processes. However, its role in lymphatic diseases had not been widely explored. We aimed to reveal the role of miR-126 in lymphangiogenesis and the regulatory signaling pathways for potential targets of therapy. APPROACH AND RESULTS: Loss-of-function studies using morpholino oligonucleotides and CRISPR/Cas9 system showed that silencing of miR-126a severely affected the formation of parachordal lymphangioblasts and thoracic duct in zebrafish embryos, although their development in miR-126b knockdown embryos was normal...
October 27, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27777406/zebrafish-as-a-new-model-to-study-effects-of-periodontal-pathogens-on-cardiovascular-diseases
#17
Magdalena Widziolek, Tomasz K Prajsnar, Simon Tazzyman, Graham P Stafford, Jan Potempa, Craig Murdoch
Porphyromonas gingivalis (Pg) is a keystone pathogen in the aetiology of chronic periodontitis. However, recent evidence suggests that the bacterium is also able to enter the bloodstream, interact with host cells and tissues, and ultimately contribute to the pathogenesis of cardiovascular disease (CVD). Here we established a novel zebrafish larvae systemic infection model showing that Pg rapidly adheres to and penetrates the zebrafish vascular endothelium causing a dose- and time-dependent mortality with associated development of pericardial oedemas and cardiac damage...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27764797/aberrant-cerna-mediated-regulation-of-kng1-contributes-to-glioblastoma-induced-angiogenesis
#18
Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27756875/eriocalyxin-b-a-natural-diterpenoid-inhibited-vegf-induced-angiogenesis-and-diminished-angiogenesis-dependent-breast-tumor-growth-by-suppressing-vegfr-2-signaling
#19
Xunian Zhou, Grace Gar-Lee Yue, Minghua Liu, Zhili Zuo, Julia Kin-Ming Lee, Mingyue Li, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27717148/a-macrocyclic-ruthenium-iii-complex-inhibits-angiogenesis-with-down-regulation-of-vascular-endothelial-growth-factor-receptor-2-and-suppresses-tumor-growth-in-vivo
#20
Wai-Lun Kwong, Kar-Yee Lam, Chun-Nam Lok, Yau-Tsz Lai, Pui-Yan Lee, Chi-Ming Che
A macrocyclic ruthenium(III) complex [Ru(III) (N2 O2 )Cl2 ]Cl (Ru-1) is reported as an inhibitor of angiogenesis and an anti-tumor compound. The complex is relatively non-cytotoxic towards endothelial and cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti-cancer ruthenium complexes, Ru-1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor-2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis...
October 17, 2016: Angewandte Chemie
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