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Endothelia

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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
#1
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/27878608/claudins-in-barrier-and-transport-function-the-kidney
#2
REVIEW
Yongfeng Gong, Jianghui Hou
Claudins are discovered to be key players in renal epithelial physiology. They are involved in developmental, physiological, and pathophysiological differentiation. In the glomerular podocytes, claudin-1 is an important determinant of cell junction fate. In the proximal tubule, claudin-2 plays important roles in paracellular salt reabsorption. In the thick ascending limb, claudin-14, -16, and -19 regulate the paracellular reabsorption of calcium and magnesium. Recessive mutations in claudin-16 or -19 cause an inherited calcium and magnesium losing disease...
November 23, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27852610/vascular-endothelium-in-diabetes
#3
Michael S Goligorsky
Three decades ago a revolutionary idea ascribing to dysfunctional endothelia some manifestations of diabetes was born, the Steno hypothesis. Here I briefly outline the accomplishments made in the past 15 years to buttress this hypothesis. Those include development of novel technological platforms to examine microcirculatory beds, deeper understanding of patterns of microvascular derangement in diabetes, pathophysiology of nitric oxide synthesis and availability, nitrosative and oxidative stress in diabetes, premature senescence of endothelial cells and the role of sirtuin 1 and lysosomal dysfunction in this process, state of endothelial glycocalyx and endothelial progenitor cells in diabetes...
November 16, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27826372/vascular-inflammation-a-novel-access-route-for-nanomedicine
#4
Roberto Molinaro, Christian Boada, Guillermo Medrano Del Rosal, Kelly A Hartman, Claudia Corbo, Elizabeth D Andrews, Naama E Toledano-Furman, John P Cooke, Ennio Tasciotti
Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD...
September 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/27792001/angiogenic-potential-of-endothelial-and-tumor-cells-seeded-on-gelatin-based-hydrogels-in-response-to-electrical-stimulations
#5
Rumiana Tzoneva, Veselina Uzunova, Sonia Apostolova, Anne Krüger-Genge, Axel T Neffe, Friedrich Jung, Andreas Lendlein
Angiogenesis is one of the key processes during development, wound healing and tumor formation. Prerequisite for its existence is the presence of endogenous electrical fields (EFs) generated by active ion transport across polarized epithelia and endothelia, and appearance of the transcellular potentials. During angiogenesis cellular factor as endothelial growth factor (VEGF), synthesis of adhesive proteins and membrane metalloproteinases (MMPs) govern the angiogenic response to different external stimuli as biomaterials interactions and/or exogenous EF...
October 27, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27751443/inflammation-and-lymphedema-are-exacerbated-and-prolonged-by-neuropilin-2-deficiency
#6
Patrick Mucka, Nicholas Levonyak, Elena Geretti, Bernadette M M Zwaans, Xiaoran Li, Irit Adini, Michael Klagsbrun, Rosalyn M Adam, Diane R Bielenberg
The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well...
October 12, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27747290/adora2b-signaling-in-cardioprotection
#7
Jennifer Gile, Tobias Eckle
Cardiovascular disease is the number one cause of death worldwide. A powerful strategy for cardioprotection would be to identify specific molecules or targets that mimic ischemic preconditioning (IP), where short non-lethal episodes of ischemia and reperfusion prior to myocardial infarction result in dramatic reduction of infarct sizes. Since 1960 researchers believed that adenosine has a strong cardio-protective potential. In fact, with the discovery of cardiac IP in 1986 by Murry et al., adenosine was the first identified molecule that was used in studying the underlying mechanism of IP...
2016: Journal of Nature and Science
https://www.readbyqxmd.com/read/27700119/biomimetic-apoe-reconstituted-high-density-lipoprotein-nanocarrier-for-blood-brain-barrier-penetration-and-amyloid-beta-targeting-drug-delivery
#8
Qingxiang Song, Huahua Song, Jianrong Xu, Jialin Huang, Meng Hu, Xiao Gu, Juan Chen, Gang Zheng, Hongzhuan Chen, Xiaoling Gao
Amyloid beta (Aβ) and its aggregation forms in the brain have been suggested as key targets for the therapy of Alzheimer's disease (AD). Therefore, the development of nanocarriers which possess both blood-brain barrier permeability and Aβ-targeting ability is of great importance for the intervention of AD. Here we constructed a biomimetic nanocarrier named apolipoprotein E (ApoE)-reconstituted high density lipoprotein nanocarrier (ANC) from recombinant ApoE and synthetic lipids to achieve the above goals...
October 4, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27640146/endothelin-1-treatment-induces-an-experimental-cerebral-malaria-like-syndrome-in-c57bl-6-mice-infected-with-plasmodium-berghei-nk65
#9
Yuri C Martins, Brandi D Freeman, Oscar B Akide Ndunge, Louis M Weiss, Herbert B Tanowitz, Mahalia S Desruisseaux
Plasmodium berghei ANKA infection of C57BL/6 mice is a widely used model of experimental cerebral malaria (ECM). By contrast, the nonneurotropic P. berghei NK65 (PbN) causes severe malarial disease in C57BL/6 mice but does not cause ECM. Previous studies suggest that endothelin-1 (ET-1) contributes to the pathogenesis of ECM. In this study, we characterize the role of ET-1 on ECM vascular dysfunction. Mice infected with 10(6) PbN-parasitized red blood cells were treated with either ET-1 or saline from 2 to 8 days postinfection (dpi)...
November 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27624938/calcium-signaling-is-dispensable-for-receptor-regulation-of-endothelial-barrier-function
#10
Judith A Stolwijk, Xuexin Zhang, Maxime Gueguinou, Wei Zhang, Khalid Matrougui, Christian Renken, Mohamed Trebak
Endothelial barrier function is tightly regulated by plasma membrane receptors and is crucial for tissue fluid homeostasis; its dysfunction causes disease, including sepsis and inflammation. The ubiquitous activation of Ca(2+) signaling upon phospholipase C-coupled receptor ligation leads quite naturally to the assumption that Ca(2+) signaling is required for receptor-regulated endothelial barrier function. This widespread hypothesis draws analogy from smooth muscle and proposes the requirement of G protein-coupled receptor (GPCR)-generated Ca(2+) signaling in activating the endothelial contractile apparatus and generating interendothelial gaps...
October 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27613541/influence-of-blood-brain-barrier-permeability-on-o-2-18-f-fluoroethyl-l-tyrosine-uptake-in-rat-gliomas
#11
Carina Stegmayr, Ulrike Bandelow, Dennis Oliveira, Philipp Lohmann, Antje Willuweit, Christian Filss, Norbert Galldiks, Joachim H R Lübke, N Jon Shah, Johannes Ermert, Karl-Josef Langen
PURPOSE: O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on (18)F-FET uptake in two rat glioma models and one human xenograft model. METHODS: F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex)...
September 9, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27603666/src-family-kinases-modulate-the-loss-of-endothelial-barrier-function-in-response-to-tnf-%C3%AE-crosstalk-with-p38-signaling
#12
Alejandro P Adam, Anthony M Lowery, Nina Martino, Hiba Alsaffar, Peter A Vincent
Activation of Src Family Kinase (SFK) signaling is required for the increase in endothelial permeability induced by a variety of cytokines and growth factors. However, we previously demonstrated that activation of endogenous SFKs by expression of dominant negative C-terminal Src Kinase (DN-Csk) is not sufficient to decrease endothelial adherens junction integrity. Basal SFK activity has been observed in normal venular endothelia and was not associated with increased basal permeability. The basal SFK activity however was found to contribute to increased sensitivity of the venular endothelium to inflammatory mediator-induced leakage...
2016: PloS One
https://www.readbyqxmd.com/read/27584788/kinsenoside-screening-with-a-microfluidic-chip-attenuates-gouty-arthritis-through-inactivating-nf-%C3%AE%C2%BAb-signaling-in-macrophages-and-protecting-endothelial-cells
#13
Qiao Han, Wang Bing, Yin Di, Li Hua, Li Shi-He, Zheng Yu-Hua, Han Xiu-Guo, Wang Yu-Gang, Fan Qi-Ming, Yang Shih-Mo, Tang Ting-Ting
Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27581465/gastric-cancer-current-and-evolving-treatment-landscape
#14
REVIEW
Weijing Sun, Li Yan
Gastric (including gastroesophageal junction) cancer is the third leading cause of cancer-related death in the world. In China, an estimated 420,000 patients were diagnosed with gastric cancer in 2011, ranking this malignancy the second most prevalent cancer type and resulting in near 300,000 deaths. The treatment landscape of gastric cancer has evolved in recent years. Although systemic chemotherapy is still the mainstay treatment of metastatic disease, the introduction of agents targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor/vascular endothelia growth factor receptor has brought this disease into the molecular and personalized medicine era...
August 31, 2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/27581191/sparc-expression-by-cerebral-microvascular-endothelial-cells-in-vitro-and-its-influence-on-blood-brain-barrier-properties
#15
Samir Alkabie, Jayasree Basivireddy, Lixin Zhou, Jane Roskams, Peter Rieckmann, Jacqueline A Quandt
BACKGROUND: SPARC (secreted protein acidic and rich in cysteine) is a nonstructural, cell-matrix modulating protein involved in angiogenesis and endothelial barrier function, yet its potential role in cerebrovascular development, inflammation, and repair in the central nervous system (CNS) remains undetermined. METHODS: This study examines SPARC expression in cultured human cerebral microvascular endothelial cells (hCMEC/D3)-an in vitro model of the blood-brain barrier (BBB)-as they transition between proliferative and barrier phenotypes and encounter pro-inflammatory stimuli...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27580018/havcr-1-involvement-in-cancer-progression
#16
Emily J A Telford, Wen G Jiang, Tracey A Martin
Formerly known for its importance in the immune system and kidney regeneration, it is becoming more apparent that HAVcR-1 an important protein in cancer biology. HAVcR-1 is overexpressed in numerous cancers and associates with critical molecules of tight junctions. Tight junctions are critical in homeostasis of cellular compartments via the maintenance of epithelia and endothelia however it has also be suggested that via the prevention of dissemination, intravasation and extravasation, tight junctions play a critical role in the prevention of cancer metastasis...
August 31, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27574007/atorvastatin-attenuates-p%C3%A2-cresyl-sulfate%C3%A2-induced-atherogenesis-and-plaque-instability-in-apoe-knockout-mice
#17
Hui Han, Yanjia Chen, Jinzhou Zhu, Jingwei Ni, Jiateng Sun, Ruiyan Zhang
p-cresyl sulfate (PCS) is a protein-bound uremic toxin retained in the blood of patients with chronic kidney disease (CKD) As atherosclerosis is a primary cardiovascular complication for patients with CKD, the aim of the present study was to investigate the mechanisms underlying the aggravation of atherosclerosis by PCS. In addition, the effect of atorvastatin was assessed in reversing the effects of PCS. PCS was revealed to promote the initiation and progression of atherosclerosis. Following treatment with atorvastatin, apolipoprotein E knockout mice demonstrated a reduction in PCS‑induced atherogenesis and plaque vulnerability...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27568563/biomechanics-of-borrelia-burgdorferi-vascular-interactions
#18
Rhodaba Ebady, Alexandra F Niddam, Anna E Boczula, Yae Ram Kim, Nupur Gupta, Tian Tian Tang, Tanya Odisho, Hui Zhi, Craig A Simmons, Jon T Skare, Tara J Moriarty
Systemic dissemination of microbes is critical for progression of many infectious diseases and is associated with most mortality due to bacterial infection. The physical mechanisms mediating a key dissemination step, bacterial association with vascular endothelia in blood vessels, remain unknown. Here, we show that endothelial interactions of the Lyme disease spirochete Borrelia burgdorferi under physiological shear stress mechanistically resemble selectin-dependent leukocyte rolling. Specifically, these interactions are mediated by transfer of mechanical load along a series of adhesion complexes and are stabilized by tethers and catch bond properties of the bacterial adhesin BBK32...
September 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27562067/the-effects-of-different-aerobic-exercise-intensities-on-serum-serotonin-concentrations-and-their-association-with-stroop-task-performance-a-randomized-controlled-trial
#19
Philipp Zimmer, Christian Stritt, Wilhelm Bloch, Frank-Peter Schmidt, Sven Thorsten Hübner, Stephan Binnebößel, Alexander Schenk, Max Oberste
PURPOSE: Acute exercise improves selective aspects of cognition such as executive functioning. Animal studies suggest that some effects are based on exercise-induced alterations in serotonin (5-HT) secretion. This study evaluates the impact of different aerobic exercise intensities on 5-HT serum levels as well as on executive functioning considering 5-HT as a potential mediator. METHODS: 121 young adults (23.8 ± 3.6 years) were examined in a randomized controlled trial including three exercise intervention (35 min) groups (low intensity, 45 % of the maximal heart rate (HRmax); moderate intensity, 65 % HRmax; high intensity, 85 % HRmax) and one control group...
October 2016: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/27560685/transport-of-gold-nanoparticles-by-vascular-endothelium-from-different-human-tissues
#20
Radka Gromnicova, Mehmet Kaya, Ignacio A Romero, Phil Williams, Simon Satchell, Basil Sharrack, David Male
The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia. Kidney endothelium (ciGENC) showed higher uptake of these nanoparticles than brain endothelium (hCMEC/D3), reflecting their biodistribution in vivo...
2016: PloS One
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