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Lymphangiogenesis

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https://www.readbyqxmd.com/read/28320855/salt-sensitivity-of-angiogenesis-inhibition-induced-blood-pressure-rise-role-of-interstitial-sodium-accumulation
#1
Stephanie Lankhorst, David Severs, Lajos Markó, Natalia Rakova, Jens Titze, Dominik N Müller, A H Jan Danser, Anton H van den Meiracker
In response to salt loading, Na(+) and Cl(-) accumulate in the skin in excess of water, stimulating skin lymphangiogenesis via activation of the mononuclear phagocyte system cell-derived vascular endothelial growth factor-C-vascular endothelial growth factor type 3 receptor signaling pathway. Inhibition of this pathway results in salt-sensitive hypertension. Sunitinib is an antiangiogenic, anticancer agent that blocks all 3 vascular endothelial growth factor receptors and increases blood pressure. We explored the salt dependency of sunitinib-induced hypertension and whether impairment of skin lymphangiogenesis is an underlying mechanism...
March 20, 2017: Hypertension
https://www.readbyqxmd.com/read/28314255/anti-metastatic-efficacy-of-traditional-chinese-medicine-tcm-ginsenoside-conjugated-to-a-vefgr-3-antibody-on-human-gastric-cancer-in-an-orthotopic-mouse-model
#2
Xiaojun Dai, Dongmei Liu, Moxiang Liu, Xiaochun Zhang, Weiming Wang, Feng Jin, Yayun Qian, Xuanyi Wang, Jingjing Zhao, Yongjian Wu, Fangfang Xiong, N A Chang, Y U Sun, Zhijian Yang, Robert M Hoffman, Yanqing Liu
Background/Aim: The aim of the present study was to investigate the efficacy of a traditional Chinese medicine (TCM), VEGFR-3 antibody-conjugated ginsenoside Rg3nanoemulsion (VRIN), targeting lymphangiogenesis, on the inhibition of tumor growth and metastasis in an orthotopic mouse model of human gastric cancer. Materials and Methods: An orthotopic nude-mouse model of gastric cancer was established with the red fluorescent protein (RFP)-expressing human gastric cancer cell line NUGC-4-RFP. The tumor-bearing mice were treated with vehicle (0...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303937/vitamin-d-inhibits-lymphangiogenesis-through-vdr-dependent-mechanisms
#3
Saleh Yazdani, Fariba Poosti, Luis Toro, Johannes Wedel, Rik Mencke, Katarina Mirković, Martin H de Borst, J Steven Alexander, Gerjan Navis, Harry van Goor, Jacob van den Born, Jan-Luuk Hillebrands
Excessive lymphangiogenesis is associated with cancer progression and renal disease. Attenuation of lymphangiogenesis might represent a novel strategy to target disease progression although clinically approved anti-lymphangiogenic drugs are not available yet. VitaminD(VitD)-deficiency is associated with increased cancer risk and chronic kidney disease. Presently, effects of VitD on lymphangiogenesis are unknown. Given the apparently protective effects of VitD and the deleterious associations of lymphangiogenesis with renal disease, we here tested the hypothesis that VitD has direct anti-lymphangiogenic effects in vitro and is able to attenuate lymphangiogenesis in vivo...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298294/vegfr3-modulates-vascular-permeability-by-controlling-vegf-vegfr2-signaling
#4
Krista Heinolainen, Sinem Karaman, Gabriela D'Amico, Tuomas Tammela, Raija Sormunen, Lauri Eklund, Kari Alitalo, Georgia Zarkada
Rationale: Vascular endothelial growth factor (VEGF) is the main driver of angiogenesis and vascular permeability via VEGF receptor 2 (VEGFR2), while lymphangiogenesis signals are transduced by VEGFC/D via VEGFR3. VEGFR3 also regulates sprouting angiogenesis and blood vessel growth, but to what extent VEGFR3 signaling controls blood vessel permeability remains unknown. Objective: To investigate the role of VEGFR3 in the regulation of VEGF-induced vascular permeability. Methods and Results: Long-term global Vegfr3 gene deletion in adult mice resulted in increased fibrinogen deposition in lungs and kidneys, indicating enhanced vascular leakage at the steady state...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28295868/ciap2-promotes-gallbladder-cancer-invasion-and-lymphangiogenesis-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#5
Xiaojie Jiang, Chengzong Li, Bin Lin, Haijie Hong, Lei Jiang, Siyuan Zhu, Xiaoqian Wang, Nanhong Tang, Xiujin Li, Feifei She, Chen Yanling
Several studies have produced contradictory findings about the prognostic implications for inhibitor of apoptosis proteins (IAPs) in different types of cancer. Cellular inhibitor of apoptosis 2 (cIAP2/BIRC) is one of the most extensively characterized human IAPs. To date no studies have focused on the expression level of cIAP2 in human gallbladder cancer (GBC), and the mechanism of cIAP2 in GBC invasion and lymphangiogenesis remains unclear. Therefore, in the present study, cIAP2 expression in GBC was detected using qRT-PCR and immunohistochemistry, and the relationship between cIAP2 levels in cancer tissues and the clinicopathological characteristics of patients was analysed...
March 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/28261022/emerging-roles-of-lymphatic-vasculature-in-immunity
#6
REVIEW
Ki-Wook Kim, Joo-Hye Song
The lymphatic vasculature has been regarded as a passive conduit for interstitial fluid and responsible for the absorption of macromolecules such as proteins or lipids and transport of nutrients from food. However, emerging data show that the lymphatic vasculature system plays an important role in immune modulation. One of its major roles is to coordinate antigen transport and immune-cell trafficking from peripheral tissues to secondary lymphoid organs, lymph nodes. This perspective was recently updated with the notion that the interaction between lymphatic endothelial cells and leukocytes controls the immune-cell migration and immune responses by regulating lymphatic flow and various secreted molecules such as chemokines and cytokines...
February 2017: Immune Network
https://www.readbyqxmd.com/read/28253401/netrin-4-mediates-corneal-hemangiogenesis-but-not-lymphangiogenesis-in-the-mouse-model-of-suture-induced-neovascularization
#7
Anna-Karina B Maier, Sabrina Klein, Norbert Kociok, Aline I Riechardt, Enken Gundlach, Nadine Reichhart, Olaf Strauß, Antonia M Joussen
Purpose: Netrin-4, a secreted protein, is found in the basement membrane of blood vessels and acts as a key regulator of angiogenesis. Here we investigated the role of Netrin-4 in the mouse-model of suture-induced corneal hem- and lymphangiogenesis. Methods: Corneal hem- and lymphangiogenesis were induced in Netrin-4-deficient (Ntn4-/-) and wild-type (WT) mice by placing three 11-0 nylon sutures intrastromally. Fourteen days after suturing, the vascularized area was analyzed via corneal flat mount immunohistochemistry...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28251313/the-role-of-macrophages-in-hypertension-and-its-complications
#8
REVIEW
A Justin Rucker, Steven D Crowley
Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent disease associated with catastrophic cardiovascular morbidity. In the vasculature and kidney, macrophage-derived reactive oxygen species (ROS) and inflammatory cytokines induce endothelial and epithelial dysfunction, respectively, resulting in vascular oxidative stress and impairment of sodium excretion. By contrast, VEGF-C-expressing macrophages in the skin can facilitate the removal of excess interstitial stores of sodium by stimulating lymphangiogenesis...
March 1, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28251217/lymphangiogenesis-and-colorectal-cancer
#9
Ciyou Huang, Yigang Chen
Lymphatic metastasis is an important event in the progress of metastasis in colorectal cancer (CRC). The purpose of this article is to assess the role of lymphangiogenesis on CRC. In peritumoral areas of CRC, the lymphatic microvessel density (LMVD) is higher than those in normal colorectal tissues. Morever, the high LMVD is correlated with DFS and local recurrence in CRC. The VEGF-C/VEGF-D/VEGFR-3 pathway, sonic hedgehog (Shh) signaling pathway and extracellular matrix (ECM) are involved in the regulation of lymphangiogenesis in CRC...
March 2017: Saudi Medical Journal
https://www.readbyqxmd.com/read/28248931/systematic-high-content-genome-wide-rnai-screens-of-endothelial-cell-migration-and-morphology
#10
Steven P Williams, Cathryn M Gould, Cameron J Nowell, Tara Karnezis, Marc G Achen, Kaylene J Simpson, Steven A Stacker
Many cell types undergo migration during embryogenesis and disease. Endothelial cells line blood vessels and lymphatics, which migrate during development as part of angiogenesis, lymphangiogenesis and other types of vessel remodelling. These processes are also important in wound healing, cancer metastasis and cardiovascular conditions. However, the molecular control of endothelial cell migration is poorly understood. Here, we present a dataset containing siRNA screens that identify known and novel components of signalling pathways regulating migration of lymphatic endothelial cells...
March 1, 2017: Scientific Data
https://www.readbyqxmd.com/read/28228406/renal-inflammation-and-injury-is-associated-with-lymphangiogenesis-in-hypertension
#11
Sterling C Kneedler, Lauren E Phillips, Kayla R Hudson, Katharine M Beckman, Catalina A Lopez Gelston, Joseph M Rutkowski, Alan R Parrish, Peter A Doris, Brett M Mitchell
Lymphatic vessels are vital for the trafficking of immune cells from the interstitium to draining lymph nodes during inflammation. Hypertension is associated with renal infiltration of activated immune cells and inflammation, however it is unknown how renal lymphatic vessels change in hypertension. We hypothesized that renal macrophage infiltration and inflammation would cause increased lymphatic vessel density in hypertensive rats. Spontaneously hypertensive rats (SHR) that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased renal lymphatic vessel density and macrophages at 40 weeks of age compared to Wistar-Kyoto (WKY) controls...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#12
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28205389/growth-inhibition-of-formed-corneal-neovascularization-following-fosaprepitant-treatment
#13
Fabio Bignami, Anna Lorusso, Paolo Rama, Giulio Ferrari
PURPOSE: The aim of this study was to test the efficacy of Neurokinin-1 Receptor (NK-1R) antagonist -Fosaprepitant- in inducing regression of established corneal neovascularization (CNV). METHODS: Twenty C57BL/6 mice underwent alkali burn. Seven days later, when corneal neovessels had developed, they received Fosaprepitant 10 mg/ml, administered topically six times a day in the right eye for 10 days. In parallel, a group of 20 causticated mice was treated with normal saline, as control...
February 15, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28188790/the-role-of-elk3-to-regulate-peritumoral-lymphangiogenesis-and-vegf-c-production-in-triple-negative-breast-cancer-cells
#14
Nuri Oh, Ji-In Park, Ji-Hoon Park, Kwang-Soo Kim, Dong Ryul Lee, Kyung-Soon Park
Tumor-induced lymphangiogenesis, a major conduit for cancer cell dissemination from the primary tumor site to lymph nodes and beyond, eventually leads to metastasis in cancer patients. Given the recent evidence revealing that the suppression of ELK3 inhibits the metastasis of triple-negative breast cancer cells, we aimed to study the underlying mechanism of impaired metastasis in ELK3-suppressed MDA-MB-231 cells (ELK3 KD) with regard to lymphangiogenesis. We found that the secretome of ELK3 KD cells inhibited tube formation, whereas it promoted the migration and invasion of lymphatic endothelial cells (LECs) in vitro...
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28186091/topical-tacrolimus-for-the-treatment-of-secondary-lymphedema
#15
Jason C Gardenier, Raghu P Kataru, Geoffrey E Hespe, Ira L Savetsky, Jeremy S Torrisi, Gabriela D García Nores, Dawit K Jowhar, Matthew D Nitti, Ryan C Schofield, Dean C Carlow, Babak J Mehrara
Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28183530/tnf%C3%AE-are-mice-display-abnormal-lymphatics-and-develop-tertiary-lymphoid-organs-in-the-mesentery
#16
Sonia Rehal, Pierre-Yves von der Weid
Chronic inflammatory diseases are associated with a persistent and enhanced response to environmental antigens. As an adaptive response to this exaggerated immune state, affected tissue typically develops tertiary lymphoid organs. Studies of Crohn disease (CD), a chronic inflammatory disease of the intestinal tract, report tertiary lymphoid organs present within the mucosal wall, along with other lymphatic diseases, such as lymphangiogenesis and obstructed lymphatic vessels. These observations suggest that downstream mesenteric lymphatic vessels and lymph drainage into mesenteric lymph nodes may be compromised...
February 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28179432/an-evolutionarily-conserved-role-for-polydom-svep1-during-lymphatic-vessel-formation
#17
Terhi Kärpanen, Yvonne Padberg, Serge A van de Pavert, Cathrin Dierkes, Nanami Morooka, Josi Peterson-Maduro, Glenn van de Hoek, Max Adrian, Naoki Mochizuki, Kiyotoshi Sekiguchi, Friedemann Kiefer, Dörte Schulte, Stefan Schulte-Merker
Rationale: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. Objective: Here, we identify the secreted Polydom/Svep1 protein as essential for formation of the lymphatic vasculature. We analyzed mutants in mice and zebrafish to gain insight into the role of Polydom/Svep1 in the lymphangiogenic process. Methods and Results: Phenotypic analysis of zebrafish polydom/svep1 mutants showed a decrease in venous and lympho-venous sprouting, which leads to an increased number of intersegmental arteries...
February 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28165470/sodium-chloride-promotes-tissue-inflammation-via-osmotic-stimuli-in-subtotal-nephrectomized-mice
#18
Fumiko Sakata, Yasuhiko Ito, Masashi Mizuno, Akiho Sawai, Yasuhiro Suzuki, Takako Tomita, Mitsuhiro Tawada, Akio Tanaka, Akiyoshi Hirayama, Akihiro Sagara, Takashi Wada, Shoichi Maruyama, Tomoyoshi Soga, Seiichi Matsuo, Enyu Imai, Yoshifumi Takei
Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28163024/vascular-endothelial-growth-factor-c-induces-osteogenic-differentiation-of-human-mesenchymal-stem-cells-through-the-erk-and-runx2-pathway
#19
Juri Murakami, Masakazu Ishii, Fumio Suehiro, Kiyohide Ishihata, Norifumi Nakamura, Masahiro Nishimura
Vascular endothelial cell growth factor C (VEGF-C) is a member of the VEGF family and plays a role in a variety of biological activities including lymphangiogenesis, angiogenesis, and neurogenesis through VEGF receptor 2 (VEGFR2) and 3 (VEGFR3). However, it has not been elucidated whether VEGF-C promotes osteogenic differentiation. Herein, we investigated the effects of VEGF-C on osteogenic differentiation in human mesenchymal stem cells (MSCs) and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly increased RUNX2 expression, and led to the promotion of osteogenic marker gene expression and mineralization of MSCs...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28135127/elm-a-new-simple-and-economic-assay-to-measure-motility-of-lymphatic-endothelial-cells
#20
Fabio Torri, Patrizia Dell'Era, Emirena Garrafa
BACKGROUND: Relatively few attempts have been made to set up an assay that allows the measurement of lymphatic endothelial cells (LECs) motility. Nowadays, the most widely used methods involve adaptation of the Boyden chamber method or the wound scratch assay, both of them showing some limitations due to long and expensive setup and high variability. METHODS AND RESULTS: We propose a new, economic, and easy to setup LEC Motility (ELM) assay that will contribute to the study of lymphangiogenesis...
March 2017: Lymphatic Research and Biology
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