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https://www.readbyqxmd.com/read/28819420/loss-of-complement-factor-h-in-plasma-increases-endothelial-cell-migration
#1
Ju Liu, Josephine Hoh
Tumor growth depends on angiogenesis, the growth of new blood vessels. Complement factor H (CFH) is a plasma glycoprotein that functions as a regulator of the complement system. The aim of this study is to delineate the role of CFH in angiogenesis. A conditional null allele of the Cfh gene was generated in C57BL/6J mice by flanking the exon 3 with loxP sites. The Cfh(flox/flox) mice were crossed with Rosa26-Cre mice to obtain the mice homozygotes of Cfh deletion (Cfh(-/-)). The Cfh(-/-) mice were examined by in vivo angiogenesis assays...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818791/low-density-lipoprotein-modified-by-myeloperoxidase-oxidants-induces-endothelial-dysfunction
#2
Adrian I Abdo, Benjamin S Rayner, David M van Reyk, Clare L Hawkins
Low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) is present in atherosclerotic lesions, where it is implicated in the propagation of inflammation and acceleration of lesion development by multiple pathways, including the induction of endothelial dysfunction. Thiocyanate (SCN(-)) ions are utilised by MPO to produce the oxidant hypothiocyanous acid (HOSCN), which reacts with LDL in a different manner to HOCl. Whilst the reactivity of HOCl-modified LDL has been previously studied, the role of HOSCN in the modification of LDL in vivo is poorly defined, although emerging evidence suggests that these particles have distinct biological properties...
August 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28817646/genetic-dissection-of-endothelial-transcriptional-activity-of-zebrafish-aryl-hydrocarbon-receptors-ahrs
#3
Wade W Sugden, Roberto C Leonardo-Mendonça, Darío Acuña-Castroviejo, Arndt F Siekmann
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor conserved across phyla from flies to humans. Activated by a number of endogenous ligands and environmental toxins, studies on AHR function and gene regulation have largely focused on a toxicological perspective relating to aromatic hydrocarbons generated by human activities and the often-deleterious effects of exposure on vertebrates mediated by AHR activation. A growing body of work has highlighted the importance of AHR in physiologic processes, including immune cell differentiation and vascular patterning...
2017: PloS One
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#4
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817119/mir-1301-inhibits-hepatocellular-carcinoma-cell-migration-invasion-and-angiogenesis-by-decreasing-wnt-%C3%AE-catenin-signaling-through-targeting-bcl9
#5
Chao Yang, Yonghua Xu, Feng Cheng, Yuanchang Hu, Shikun Yang, Jianhua Rao, Xuehao Wang
Metastasis is the major cause of the poor prognosis of hepatocellular carcinoma (HCC), and increasing evidence supports the contribution of miRNAs to cancer progression. However, the exact relationship between the level of miR-1301 expression and HCC cell migration, invasion, and angiogenesis remains largely unknown. Quantitative PCR was used to evaluate the level of miR-1301 expression in HCC tissues and cell lines. Transwell and tube-formation assays were used to measure the effects of miR-1301 on HCC cell migration and invasion, and angiogenesis, respectively...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#6
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GEC), podocytes and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
August 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28814629/modular-tissue-engineering-for-the-vascularization-of-subcutaneously-transplanted-pancreatic-islets
#7
Alexander E Vlahos, Nicholas Cober, Michael V Sefton
The transplantation of pancreatic islets, following the Edmonton Protocol, is a promising treatment for type I diabetics. However, the need for multiple donors to achieve insulin independence reflects the large loss of islets that occurs when islets are infused into the portal vein. Finding a less hostile transplantation site that is both minimally invasive and able to support a large transplant volume is necessary to advance this approach. Although the s.c. site satisfies both these criteria, the site is poorly vascularized, precluding its utility...
August 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28813672/chromatin-and-transcriptional-analysis-of-mesoderm-progenitor-cells-identifies-hopx-as-a-regulator-of-primitive-hematopoiesis
#8
Nathan J Palpant, Yuliang Wang, Brandon Hadland, Rebecca J Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR(+)/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28811655/a-tissue-engineered-blood-vessel-model-of-hutchinson-gilford-progeria-syndrome-using-human-ipsc-derived-smooth-muscle-cells
#9
Leigh Atchison, Haoyue Zhang, Kan Cao, George A Truskey
Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811547/up-regulation-of-nadph-oxidase-mediated-redox-signaling-contributes-to-the-loss-of-barrier-function-in-krit1-deficient-endothelium
#10
Luca Goitre, Peter V DiStefano, Andrea Moglia, Nicholas Nobiletti, Eva Baldini, Lorenza Trabalzini, Julie Keubel, Eliana Trapani, Vladimir V Shuvaev, Vladimir R Muzykantov, Ingrid H Sarelius, Saverio Francesco Retta, Angela J Glading
The intracellular scaffold KRIT1/CCM1 is an established regulator of vascular barrier function. Loss of KRIT1 leads to decreased microvessel barrier function and to the development of the vascular disorder Cerebral Cavernous Malformation (CCM). However, how loss of KRIT1 causes the subsequent deficit in barrier function remains undefined. Previous studies have shown that loss of KRIT1 increases the production of reactive oxygen species (ROS) and exacerbates vascular permeability triggered by several inflammatory stimuli, but not TNF-α...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811219/trinucleotide-repeat-containing-6c-tnrc6c-is-essential-for-microvascular-maturation-during-distal-airspace-sacculation-in-the-developing-lung
#11
Hua Guo, Yana Kazadaeva, Fabian E Ortega, Manjunath N Swamy, Tushar J Desai
GW182 (also known asTNRC6) family members are critically involved in the final effector phase of miRNA-mediated mRNA repression. The three mammalian paralogs, TNRC6a, b and c, are thought to be redundant based on Argonaute (Ago) binding, tethering assays, and RNAi silencing of individual members in cell lines. To test this idea, we generated TNRC6a, b and c knockout mice. TNRC6a mutants die at mid-gestation, while b- and c- deleted mice are born at a Mendelian ratio. However, the majority of TNRC6b and all TNRC6c mutants die within 24 hours after birth, the latter with respiratory failure...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28810961/resuscitation-of-hypotensive-traumatic-brain-injured-animals-with-spray-dried-plasma-does-not-adversely-alter-physiology-and-improves-blood-brain-barrier-function
#12
Steven McDaniel, Stephanie Golla, Anthony N Moore, Joe DaCorta, Arthur Bode, Shibani Pati, Pramod K Dash, Jing Zhao
INTRODUCTION: According to the Defense and Veterans Brain Injury Center and the Armed Forces Health Surveillance Center, the number of soldiers who have sustained a traumatic brain injury (TBI) has risen dramatically over the past decade. Studies have shown that brain damage can be exacerbated if blood loss occurs (often occurring in polytrauma). As blood supply is critical for brain function and survival, TBI patients must be properly resuscitated to maintain blood volume, blood pressure, and cerebral perfusion...
July 2017: Military Medicine
https://www.readbyqxmd.com/read/28810657/anti-exudation-effects-of-sodium-ferulate-and-oxymatrine-combination-via-modulation-of-aquaporin-1
#13
Songmei Sun, Xing Du, Mengxin Xu, Meijuan Liu, Zhifeng Liu
The present study aimed to investigate the anti-exudative effects of sodium ferulate combined with oxymatrine in a mouse model of acetic acid-induced peritonitis. Furthermore, the underlying mechanisms were explored by determining the effects of these drugs on the volume and aquaporin 1 (AQP1) expression in vascular endothelial cells on omentum majus and human umbilical vein endothelial cells (HUVEC). Treatment with sodium ferulate combined with oxymatrine was shown to significantly inhibit acetic acid-induced vascular permeability in the peritonitis model mice and furthermore to significantly decrease the optical density of Evans blue, the leukocyte number and the levels of interleukin-6, C-reactive protein and interferon-γ in peritoneal lavage fluid...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810642/overexpressed-enos-upregulates-sirt1-expression-and-protects-mouse-pancreatic-%C3%AE-cells-from-apoptosis
#14
Tingting Hu, Ye Chen, Qian Jiang, Jun Lin, Hewei Li, Ping Wang, Leping Feng
Loss of sirtuin 1 (SIRT1) activity may be associated with metabolic diseases, including diabetes. The aim of the present study was to investigate the potential effects of overexpressed endothelial nitric oxide synthase (eNOS) on cell proliferation and apoptosis with SIRT1 activation in the Min6 mouse pancreatic β cell line. A pcDNA3.0-eNOS plasmid was constructed and transfected into Min6 cells for 24 h prior to harvesting. eNOS expression was validated and SIRT1 expression was detected following plasmid transfection using reverse transcription-quantitative polymerase chain reaction and western blot analysis, which demonstrated that the expression levels of eNOS and SIRT1 were significantly upregulated...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#15
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809959/expression-and-activity-of-angiotensin-regulating-enzymes-is-associated-with-prognostic-outcome-in-clear-cell-renal-cell-carcinoma-patients
#16
Peio Errarte, Maider Beitia, Itxaro Perez, Lorea Manterola, Charles H Lawrie, Jon Danel Solano-Iturri, Julio Calvete-Candenas, Miguel Unda, José I López, Gorka Larrinaga
The discovery of the intrarenal renin-angiotensin system (iRAS), which regulates angiogenesis, cell differentiation and proliferation, has opened new perspectives in the knowledge of kidney carcinogenesis. In this study we analyzed the immunohistochemical expression and fluorimetric activity of four key peptidases of iRAS in tumor tissue (n = 144) and serum samples (n = 128) from patients with renal neoplasms. Neutral endopeptidase (NEP/CD10), Angiotensin-converting enzyme-2 (ACE2), and aminopeptidase A (APA) were expressed in tumor cells whilst Angiotensin-converting enzyme (ACE) was expressed in the endothelial cells of intratumor blood vessels...
2017: PloS One
https://www.readbyqxmd.com/read/28809932/rem-sleep-deprivation-induces-endothelial-dysfunction-and-hypertension-in-middle-aged-rats-roles-of-the-enos-no-cgmp-pathway-and-supplementation-with-l-arginine
#17
Jiaye Jiang, Zhongyuan Gan, Yuan Li, Wenqi Zhao, Hanqing Li, Jian-Pu Zheng, Yan Ke
Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes...
2017: PloS One
https://www.readbyqxmd.com/read/28809151/the-pentameric-complex-of-human-cytomegalovirus-cell-tropism-virus-dissemination-immune-response-and-vaccine-development
#18
Giuseppe Gerna, Maria Grazia Revello, Fausto Baldanti, Elena Percivalle, Daniele Lilleri
Between the 1980s and 1990s, three assays were developed for diagnosis of human cytomegalovirus (HCMV) infections: leuko (L)-antigenemia, l-viremia and l-DNAemia, detecting viral protein pp65, infectious virus and viral DNA, respectively, in circulating leukocytes Repeated initial attempts to reproduce the three assays in vitro using laboratory-adapted strains and infected cell cultures were consistently unsuccessful. Results were totally reversed when wild-type HCMV strains were used to infect either fibroblasts or endothelial cells...
August 15, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28806945/tumor-microenvironment-conditions-alter-akt-and-na-h-exchanger-nhe1-expression-in-endothelial-cells-more-than-hypoxia-alone-implications-for-endothelial-cell-function-in-cancer
#19
A K Pedersen, J Mendes Lopes de Melo, N Mørup, K Tritsaris, S F Pedersen
BACKGROUND: Chronic angiogenesis is a hallmark of most tumors and takes place in a hostile tumor microenvironment (TME) characterized by hypoxia, low nutrient and glucose levels, elevated lactate and low pH. Despite this, most studies addressing angiogenic signaling use hypoxia as a proxy for tumor conditions. Here, we compared the effects of hypoxia and TME conditions on regulation of the Na(+)/H(+) exchanger NHE1, Ser/Thr kinases Akt1-3, and downstream effectors in endothelial cells...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28806758/developmental-vascular-remodeling-defects-and-postnatal-kidney-failure-in-mice-lacking-gpr116-adgrf5-and-eltd1-adgrl4
#20
Shun Lu, Shuya Liu, Astrid Wietelmann, Baktybek Kojonazarov, Ann Atzberger, Cong Tang, Ralph Theo Schermuly, Hermann-Josef Gröne, Stefan Offermanns
GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced...
2017: PloS One
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