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Lymphatic endothelial cell

Johanna P Laakkonen, Johanna Lähteenvuo, Suvi Jauhiainen, Tommi Heikura, Seppo Ylä-Herttuala
Vascular endothelial growth factors regulate vascular and lymphatic growth. Dysregulation of VEGF signaling is connected to many pathological states, including hemangiomas, arteriovenous malformations and placental abnormalities. In heart, VEGF gene transfer induces myocardial angiogenesis. Besides vascular and lymphatic endothelial cells, VEGFs affect multiple other cell types. Understanding VEGF biology and its paracrine signaling properties will offer new targets for novel treatments of several diseases.
October 17, 2018: Vascular Pharmacology
Piyush Pillarisetti, Kenneth A Myers
Due to its important role in regulating angiogenesis, vascular homeostasis and remodeling, and arteriogenesis in blood vascular and lymphatic endothelial cells, VEGFR2 stimulation has demonstrated promise in preclinical studies as an endovascular treatment for ischemic myocardial and peripheral disease. However, the short half-life of protein- and cytokine-based strategies and transduction inefficiency of vector-based modalities have hindered its clinical therapeutic applications. In the present study, we used a streamlined bioinformatics strategy combining ligand-based pharmacophore development and validation, virtual screening, and molecular docking to identify agnuside, a non-toxic, natural small molecule extract of Vitex agnus-castus possessing strong binding affinity, druggable physiochemical properties, and conformationally stable hydrogen bond and hydrophobic interactions with catalytically important residues within VEGFR2's active and allosteric sites...
October 5, 2018: European Journal of Medicinal Chemistry
Ivanka Temelkova, Michael Tronnier, Ivan Terziev, Uwe Wollina, Ilia Lozev, Mohamad Goldust, Georgi Tchernev
BACKGROUND: Kaposi's sarcoma was first described in 1872 by Moritz Kaposi. To date, it is considered a malignant disease is originating from the endothelial cells of the lymphatic vessels believed to be infected with HHV-8. The current classification defines four major epidemiological forms of Kaposi's sarcoma: classical, endemic, AIDS-associated, and iatrogenic. CASE REPORT: A 90-year-old male is presented with multiple plaques- and tumour-shaped brown-violet formations located on an erythematous-livid base in the area of both feet and both shanks...
September 25, 2018: Open Access Macedonian Journal of Medical Sciences
Mehdi Moustaqil, Frank Fontaine, Jeroen Overman, Alex McCann, Timothy L Bailey, Paulina Rudolffi Soto, Akshay Bhumkar, Nichole Giles, Dominic J B Hunter, Yann Gambin, Mathias Francois, Emma Sierecki
During embryogenesis, vascular development relies on a handful of transcription factors that instruct cell fate in a distinct sub-population of the endothelium (1). The SOXF proteins that comprise SOX7, 17 and 18, are molecular switches modulating arterio-venous and lymphatic endothelial differentiation (2,3). Here, we show that, in the SOX-F family, only SOX18 has the ability to switch between a monomeric and a dimeric form. We characterized the SOX18 dimer in binding assays in vitro, and using a split-GFP reporter assay in a zebrafish model system in vivo...
October 18, 2018: Nucleic Acids Research
Sara Paccosi, Astrid Parenti
Vascular remodeling is an alteration in the structure of vessels in response to injury or hemodynamic changes. Disturbance of the structural and functional integrity of the endothelial cell layer can be observed in vascular remodeling associated with inflammation. Chemokines have been implicated in a wide range of diseases with prominent inflammatory components, and also in vascular remodeling. Among them, CC-chemokines are of great interest. They act through conventional CC-chemokine receptors (CCRs), widely expressed by leucocytes and especially monocytes, which are attracted to sites of chronic inflammation...
October 17, 2018: Current Pharmaceutical Biotechnology
Boksik Cha, Xin Geng, Md Riaj Mahamud, Jenny Y Zhang, Lijuan Chen, Wantae Kim, Eek-Hoon Jho, Yeunhee Kim, Dongwon Choi, J Brandon Dixon, Hong Chen, Young-Kwon Hong, Lorin Olson, Tae Hoon Kim, Bradley J Merrill, Michael J Davis, R Sathish Srinivasan
Wnt/β-catenin signaling is necessary for lymphatic vascular development. Oscillatory shear stress (OSS) enhances Wnt/β-catenin signaling in cultured lymphatic endothelial cells (LECs) to induce expression of the lymphedema-associated transcription factors GATA2 and FOXC2. However, the mechanisms by which OSS regulates Wnt/β-catenin signaling and GATA2 and FOXC2 expression are unknown. We show that OSS activates autocrine Wnt/β-catenin signaling in LECs in vitro. Tissue-specific deletion of Wntless, which is required for the secretion of Wnt ligands, reveals that LECs and vascular smooth muscle cells are complementary sources of Wnt ligands that regulate lymphatic vascular development in vivo...
October 16, 2018: Cell Reports
Xiaofei Zhu, Yun Chen, Wenqiang Zhu, Mingde Ji, Jing Xu, Yuanyuan Guo, Feng Gao, Wanjian Gu, Xuewen Yang, Chunbing Zhang
BACKGROUND AND PURPOSE: KSHV vIL-6 is sufficient to induce lymphatic reprogramming of vascular endothelial cells, which is a key event in KS development. This study was aimed to investigate the effect of Chinese herb Oroxylin A on lymphatic reprogramming and neovascularization by KSHV vIL-6 in vitro and in vivo. METHODS: Lymphatic-phenotype endothelial cell line was generated by lentiviral KSHV vIL-6 infection. Cell viability and apoptosis was determined by MTT assay or flow cytometry with Annexin V/PI staining...
October 14, 2018: Journal of Medical Virology
Yuan-Li Huang, Yueh-Chien Lin, Chu-Cheng Lin, Wei-Min Chen, Benjamin P C Chen, Hsinyu Lee
BACKGROUND/AIMS: Hyperglycemia has been shown to increase the incidence and metastasis in various types of cancers. However, the correlation between hyperglycemia and lymphatic metastasis in prostate cancer (PCa) remains unclear. Our previous study demonstrated that lysophosphatidic acid (LPA) enhances vascular endothelial growth factor-C (VEGF-C) expression, a lymphangiogenic factor, through activating it receptors LPA1/3 in prostate cancer (PCa) cells. Moreover, hyperglycemia up-regulates autotaxin (ATX) expression, a LPA-generating enzyme...
October 12, 2018: Cellular Physiology and Biochemistry
Mirko Manetti, Sara Pratesi, Eloisa Romano, Irene Rosa, Cosimo Bruni, Silvia Bellando-Randone, Serena Guiducci, Enrico Maggi, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
No abstract text is available yet for this article.
October 12, 2018: Annals of the Rheumatic Diseases
René Hägerling, Esther Hoppe, Cathrin Dierkes, Martin Stehling, Taija Makinen, Stefan Butz, Dietmar Vestweber, Friedemann Kiefer
Endothelial cells line blood and lymphatic vessels and form intercellular junctions, which preserve vessel structure and integrity. The vascular endothelial cadherin, VE-cadherin, mediates endothelial adhesion and is indispensible for blood vessel development and permeability regulation. However, its requirement for lymphatic vessels has not been addressed. During development, VE-cadherin deletion in lymphatic endothelial cells resulted in abortive lymphangiogenesis, edema, and prenatal death. Unexpectedly, inducible postnatal or adult deletion elicited vessel bed-specific responses...
October 8, 2018: EMBO Journal
Weisong Shen, Yi Li, Yujie Zou, Lei Cao, Xingchen Cai, Jianfeng Gong, Yihan Xu, Weiming Zhu
Background: Mesenteric fat wrapping and thickening are typical characteristics of Crohn's disease (CD). The purpose of this study was to explore the cause of mesenteric adipose hypertrophy and analyze the role of lymphatic vessels in mesenteric adipose tissue in CD. Methods: Twenty-three CD patients who underwent ileocolonic resection were included. In CD patients, specimens were obtained from hypertrophic mesenteric adipose tissue (htMAT) next to the diseased ileum...
October 5, 2018: Inflammatory Bowel Diseases
Meghan Schilthuis, Seth Verkaik, Mackenzie Walhof, Andrew Philipose, Olivia Harlow, Derrick Kamp, Bo Ram Kim, Anding Shen
BACKGROUND: An HIV cure has not yet been achieved because latent viral reservoirs persist, particularly in resting CD4+ T lymphocytes. In vitro, it is difficult to infect resting CD4+ T cells with HIV-1, but infections readily occur in vivo. Endothelial cells (EC) line the lymphatic vessels in the lymphoid tissues and regularly interact with resting CD4+ T cells in vivo. Others and we have shown that EC promoted productive and latent HIV infection of resting CD4+ T cells. However, the EC used in previous studies were from human umbilical cords (HUVEC), which are macrovascular; whereas EC residing in the lymphoid tissues are microvascular...
October 3, 2018: Virology Journal
Alba Yanguas, Saray Garasa, Álvaro Teijeira, Cristina Aubá, Ignacio Melero, Ana Rouzaut
The quantity of T-lymphocytes reaching the draining lymph nodes from tumors is likely important to mount effective distant responses and for the establishment of long term systemic memory. Looking into mechanisms behind lymphocyte egress, we directed our attention to leukocyte adhesion mechanisms inside tumors. Here we demonstrate that activated T-cells form intra-tumor aggregates in a LFA-1-ICAM-1-dependent fashion in mouse models of melanoma and breast cancer. We also provide evidence of the presence of T-cell clusters in primary human melanoma...
2018: Frontiers in Immunology
Kathryn Glaser, Peter Dickie, Belinda Hsi Dickie
Kaposiform lymphangiomatosis (KLA) is a vascular anomaly featuring lymphatic expansion. It has no known cause, no effective treatment, and is associated with high morbidity. Proliferative cells from 3 KLA patient lesions were characterized relative to adiopose-derived mesenchyme stem cells (ADSCs) and cells derived from a patient with the related disease kaposiform hemangioendothelioma (KHE). KLA cells variably expressed markers of mesenchyme stem cells (CD73, CD90, CD105, CD146) and lacked endothelial cell markers (CD31, CD34) as determined by flow cytometry...
September 25, 2018: Journal of Pediatric Hematology/oncology
Rui-Cheng Ji, Yuki Eshita, Takashi Kobayashi, Shinya Hidano, Naganori Kamiyama, Yasuhiko Onishi
Lymphangiogenesis plays a crucial role in promoting cancer metastasis to sentinel lymph nodes (LNs) and beyond. Increasing data have shown that simvastatin, a cholesterol-lowering medication for the prevention of cardiovascular diseases, is involved in tumor growth and dissemination, and endothelial functions. This study aimed to investigate the potential effect of simvastatin on lymphatic formation and LN metastasis. Tumor models were established by subcutaneous injection of B16-F10 melanoma cells into mouse hind footpads...
September 25, 2018: Clinical & Experimental Metastasis
Chen-Fei Zhou, Jing Ma, Lei Huang, Hong-Yan Yi, Yan-Mei Zhang, Xiang-Guang Wu, Rui-Ming Yan, Li Liang, Mei Zhong, Yan-Hong Yu, Sha Wu, Wei Wang
Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous miRNAs array of cervical squamous cell carcinoma (CSCC) clinical specimens identified upregulation of miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis in CSCC. More importantly, miR-221-3p is characteristically enriched in and transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs migration and tube formation in vitro, and facilitate lymphangiogenesis and LN metastasis in vivo according to both gain-of-function and loss-of-function experiments...
September 25, 2018: Oncogene
Alan M Elder, Beth Aj Tamburini, Lyndsey S Crump, Sarah A Black, Veronica M Wessells, Pepper J Schedin, Virginia F Borges, Traci R Lyons
Postpartum mammary gland involution is a tissue remodeling event that occurs in all mammals in the absence of nursing or after weaning to return the gland to the pre-pregnant state. The tissue microenvironment created by involution has proven to be tumor promotional. Here we report that the GPI-linked protein semaphorin 7a (SEMA7A) is expressed on mammary epithelial cells during involution and use preclinical models to demonstrate that tumors induced during involution express high levels of SEMA7A. Overexpression of SEMA7A promoted the presence of myeloid-derived podoplanin (PDPN)-expressing cells in the tumor microenvironment and during involution...
September 25, 2018: Cancer Research
L Roncati, A Manenti, T Pusiol, E Mataca, S Nosseir, F Piscioli, A Maiorana, G Barbolini
Modern immunohistochemical techniques allow a detailed study of the lymphatic system in many organs and areas of the body. We performed an in-depth study on lymphatic vessels of the ileal and colonic mesenteries, together with the greater omentum where they appear particularly numerous and mainly represented by capillaries interconnected among themselves and with lymph nodes. The capillary wall consists of a fine single sheath of endothelial cells wrapped around by a subtle collagen membrane and deprived of valves...
2018: Lymphology
Pengchun Yu, Tiago C Alves, Richard G Kibbey, Michael Simons
Metabolism is pivotal for formation of the lymphatic vasculature. Understanding metabolism in lymphatic endothelial cells (LECs) requires quantitative characterization of specific metabolic pathways. Here we describe methods for using radioactive tracers to assess flux rates of glycolysis, fatty acid β-oxidation, glucose oxidation, and glutamine oxidation. We also provide a detailed method for utilizing mass spectrometry (MS) to measure glycolytic intermediates and ATP.
2018: Methods in Molecular Biology
Anita Rogic, Francois Auger, Mihaela Skobe
Studies of lymphangiogenesis and lymphatic endothelial biology in vitro require pure cultures of lymphatic endothelial cells and 3D vascular constructs, which closely resemble native human lymphatic vasculature. We describe a method for the isolation of human dermal microvascular lymphatic endothelial cells and generation of a 3D lymphatic capillary network. The lymphatic vascular construct is generated by coculturing primary lymphatic endothelial cells and fibroblasts in their native matrix, without the use of synthetic scaffolds or exogenous factors...
2018: Methods in Molecular Biology
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