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https://www.readbyqxmd.com/read/28515434/cerebral-blood-flow-regulation-and-neurovascular-dysfunction-in-alzheimer-disease
#1
REVIEW
Kassandra Kisler, Amy R Nelson, Axel Montagne, Berislav V Zlokovic
Cerebral blood flow (CBF) regulation is essential for normal brain function. The mammalian brain has evolved a unique mechanism for CBF control known as neurovascular coupling. This mechanism ensures a rapid increase in the rate of CBF and oxygen delivery to activated brain structures. The neurovascular unit is composed of astrocytes, mural vascular smooth muscle cells and pericytes, and endothelia, and regulates neurovascular coupling. This Review article examines the cellular and molecular mechanisms within the neurovascular unit that contribute to CBF control, and neurovascular dysfunction in neurodegenerative disorders such as Alzheimer disease...
May 18, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28472612/acidemia-and-blood-free-fatty-acids-analysis-of-cardiovascular-risk-factors-in-a-new-context
#2
António Heitor Reis
Following a hypothesis developed in an earlier paper, here it is discussed how deviations of blood pH from the normal range (namely states of acidemia) together with high blood levels of free fatty acids (FFA) may offer a rationale for many important risk factors for cardiovascular diseases (CVD) by shaping a context for formation of fatty acid micelles and vesicles with an acidic core, which fuse with the endothelia, disrupt vital cell processes, and thereby may initiate atherosclerotic plaque formation. Acidemia may arise primarily from dysregulation of the systemic buffers that control blood pH, chronic diseases of kidneys and lungs, inappropriate diet, or may be induced by some common drugs...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28467903/locally-triggered-release-of-the-chemokine-ccl21-promotes-dendritic-cell-transmigration-across-lymphatic-endothelia
#3
Kari Vaahtomeri, Markus Brown, Robert Hauschild, Ingrid De Vries, Alexander Franz Leithner, Matthias Mehling, Walter Anton Kaufmann, Michael Sixt
Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28461173/poly-adp-ribose-polymerase-1-regulates-microglia-mediated-decrease-of-endothelial-tight-junction-integrity
#4
Abbas Rezaeian Mehrabadi, Minna A Korolainen, Gary Odero G, Donald W Miller, Tiina M Kauppinen
Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aβ) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells...
April 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28461089/vascular-lesions-of-the-female-genital-tract-clinicopathologic-findings-and-application-of-the-issva-classification
#5
Georgia Karpathiou, Celine Chauleur, Vanessa Da Cruz, Fabien Forest, Michel Peoc'h
INTRODUCTION: Vascular lesions of the female genital tract are extremely rare and their nomenclature does not widely follow the International Society for the Study of Vascular Anomalies (ISSVA) classification. AIM OF THE STUDY: To describe the clinicopathologic characteristics of vascular lesions of the female genital tract and to apply the ISSVA classification. MATERIAL AND METHODS: 19 vascular lesions were diagnosed during a 20 year period...
April 23, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28431986/ninj2-a-novel-regulator-of-endothelial-inflammation-and-activation
#6
Jingjing Wang, Jingjing Fa, Pengyun Wang, Xinzhen Jia, Huixin Peng, Jing Chen, Yifan Wang, Chenhui Wang, Qiuyun Chen, Xin Tu, Qing K Wang, Chengqi Xu
Previous genetic studies suggested that variants in NINJ2 (encode ninjurin2) confer risk to ischemic stroke or large artery atherosclerotic stroke. However, the underlying mechanisms of NINJ2 in ischemic stroke or atherosclerosis are still unknown. In this study, we hypothesized that NINJ2 may play a role in endothelial inflammation and activation, and regulate the process of atherosclerosis. Here, we demonstrated that NINJ2 can regulate the expression of a panel of genes that are associated with inflammation and atherosclerosis (e...
April 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28404940/rnai-mediated-inhibition-of-lgr5-leads-to-decreased-angiogenesis-in-gastric-cancer
#7
Hong-Qing Xi, Ke-Cheng Zhang, Ji-Yang Li, Jian-Xin Cui, Yun-He Gao, Bo Wei, Dongsheng Huang, Lin Chen
Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a novel gastric cancer marker. However, it is unclear whether it can play roles in tumor angiogenesis. In this study, we aim to investigate the role of Lgr5 on gastric cancer angiogenesis. Lgr5, VEGF expression levels and microvessel density (MVD) were detected in tumor tissue. Then, Lgr5 mRNA was downregulated by small interference RNA technique. Western blotting and real-time quantitative PCR (qRT-PCR) were performed to detect the expression of Lgr5 and VEGF protein and mRNA in Lgr5 siRNA-transfected gastric cancer cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403507/endothelial-dysfunction-and-mechanobiology-in-pathological-cutaneous-scarring-lessons-learned-from-soft-tissue-fibrosis
#8
REVIEW
C Huang, L Liu, Z You, Y Zhao, J Dong, Y Du, R Ogawa
Hypertrophic scars/keloids are pathogenic scars that are characterized by collagen and fibroblast accumulation. The endothelia in the lesions are mechanosensitive and participate actively in the pathogenesis of these scars. The present review summarizes how endothelium responds to mechanical stimuli such as shear, stretch, and hydrostatic pressure. It also shows that in heart, liver, kidney, and lung fibrosis, endothelial dysfunctions (EDs) associate with changes in vascular tone, endothelial permeability, coagulation, and vasomodulation that result in inflammation, hypertension, and coagulation...
April 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28396443/plasma-fibronectin-stabilizes-borrelia-burgdorferi-endothelial-interactions-under-vascular-shear-stress-by-a-catch-bond-mechanism
#9
Alexandra F Niddam, Rhodaba Ebady, Anil Bansal, Anne Koehler, Boris Hinz, Tara J Moriarty
Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with endothelia under vascular shear stress requires mechanically specialized interaction mechanisms, including force-strengthened catch bonds. However, the biomechanical mechanisms supporting vascular interactions of most bacterial pathogens are undefined...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28389777/contribution-of-tumor-endothelial-cells-to-drug-resistance-anti-angiogenic-tyrosine-kinase-inhibitors-act-as-p-glycoprotein-antagonists
#10
MariaRosa Bani, Alessandra Decio, Raffaella Giavazzi, Carmen Ghilardi
Tumor endothelial cells (TEC) differ from the normal counterpart, in both gene expression and functionality. TEC may acquire drug resistance, a characteristic that is maintained in vitro. There is evidence that TEC are more resistant to chemotherapeutic drugs, substrates of ATP-binding cassette (ABC) transporters. TEC express p-glycoprotein (encoded by ABCB1), while no difference in other ABC transporters was revealed compared to normal endothelia. A class of tyrosine kinase inhibitors (TKI), used as angiostatic compounds, interferes with the ATPase activity of p-glycoprotein, thus impairing its functionality...
April 7, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28377744/non-neuronal-cells-in-the-hypothalamic-adaptation-to-metabolic-signals
#11
REVIEW
Alejandra Freire-Regatillo, Pilar Argente-Arizón, Jesús Argente, Luis Miguel García-Segura, Julie A Chowen
Although the brain is composed of numerous cell types, neurons have received the vast majority of attention in the attempt to understand how this organ functions. Neurons are indeed fundamental but, in order for them to function correctly, they rely on the surrounding "non-neuronal" cells. These different cell types, which include glia, epithelial cells, pericytes, and endothelia, supply essential substances to neurons, in addition to protecting them from dangerous substances and situations. Moreover, it is now clear that non-neuronal cells can also actively participate in determining neuronal signaling outcomes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28349484/in-vitro-and-ex-vivo-models-to-study-t-cell-migration-through-the-human-liver-parenchyma
#12
Benjamin G Wiggins, Konstantinos Aliazis, Scott P Davies, Gideon Hirschfield, Patricia F Lalor, Gary Reynolds, Zania Stamataki
The liver is the largest internal organ and filters around 3 pints of blood per minute. This continuous flux of blood should not be confused with rapid egress of lymphocytes through the liver; this organ has intricate corridors of specialized sinusoidal spaces, ensuring that immune cells decelerate to shear flow rates, and providing ample opportunities to interact with parenchymal cells. Migration has been intricately linked to T cell function; it is therefore important to study liver T cell biology into context within the liver microenvironment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28347692/mir-21-5p-203a-3p-promote-ox-ldl-induced-endothelial-cell-senescence-through-down-regulation-of-mitochondrial-fission-protein-drp1
#13
Jie-Jie Zhang, Wei-Qi Liu, Jing-Jie Peng, Qi-Lin Ma, Jun Peng, Xiu-Ju Luo
This study aims to identify both endothelia-specific/enriched and senescence-associated miRNAs as well as their functions. The rats were fed on high-fat diet to establish a hyperlipidemic model, which showed an increase in plasma lipids and acceleration in endothelial senescence and endothelial dysfunction, accompanied by alterations in 7 endothelia-specific/enriched and senescence-associated miRNAs. Among the 7 selected miRNAs, miR-21-5p and miR-203a-3p were significantly up-regulated in a human umbilical vein endothelial cells (HUVECs) senescent model induced by ox-LDL, consistent with their changes in the hyperlipidemic rats...
March 24, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28343945/as-human-lung-microvascular-endothelia-achieve-confluence-src-family-kinases-are-activated-and-tyrosine-phosphorylated-p120-catenin-physically-couples-neu1-sialidase-to-cd31
#14
Sang W Hyun, Anguo Liu, Zhenguo Liu, Erik P Lillehoj, Joseph A Madri, Albert B Reynolds, Simeon E Goldblum
In postconfluent human pulmonary microvascular endothelial cell (HPMEC)s, NEU1 sialidase associates with and desialylates the src family kinase (SFK) substrate, CD31, and disrupts angiogenesis. We asked whether the NEU1-CD31 interaction might be SFK-driven. We found that normalized phospho-SFK (PY416) signal is increased in postconfluent HPMECs compared to subconfluent cells and prior SFK inhibition with PP2 or SU6656 completely blocked NEU1 association with and desialylation of CD31. Prior silencing of each of the four SFKs expressed in HPMECs, as well as CD31, dramatically reduced confluence-induced SFK activation...
March 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28342848/ultraviolet-a-induced-oxidation-in-cornea-characterization-of-the-early-oxidation-related-events
#15
Corinne Zinflou, Patrick J Rochette
Exposure to sunlight ultraviolet-A (UVA), the main component of solar UV reaching the eyes, is suspected to play an important part in the onset of ocular pathologies. UVA primary biological deleterious effects arise from the photo-induction of oxidative stress in cells. However, the molecular bases linking UVA-induced oxidation to UVA toxicity in eyes remain poorly understood, especially with regards to the cornea. To shed some light on this issue, we have investigated the susceptibility and response potential of the different corneal cellular layers (epithelium, stroma and endothelium) to UVA-induced oxidation...
March 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28296822/the-different-effects-of-vegfa121-and-vegfa165-on-regulating-angiogenesis-depend-on-phosphorylation-sites-of-vegfr2
#16
Wang Shiying, Sun Boyun, Yuan Jianye, Zhang Wanjun, Tao Ping, Lin Jiang, Hu Hongyi
The effects of VEGFA isoforms on the vascular permeability and structure are still unclear. In this study, we found that VEGFA121 and VEGFA165, 2 isoforms of VEGFA, exerted the opposing effects of antiangiogenesis and proangiogenesis on regulating vascular endothelia cells proliferation and tube formation. The 2 isoforms affected the protein expression of Ras-related protein 1-GTPase-activating protein 1 (Rap1GAP) and thrombospondin 1, 2 important signal molecules of Rap1GAP/thrombospondin 1 signal pathway in primary human umbilical vein endothelial cells by regulating 2 different phosphorylating sites of VEGFR2, Tyr(1175) and Tyr(1214)...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28288111/gpr124-is-essential-for-blood-brain-barrier-integrity-in-central-nervous-system-disease
#17
Junlei Chang, Michael R Mancuso, Carolina Maier, Xibin Liang, Kanako Yuki, Lu Yang, Jeffrey W Kwong, Jing Wang, Varsha Rao, Mario Vallon, Cynthia Kosinski, J J Haijing Zhang, Amanda T Mah, Lijun Xu, Le Li, Sharareh Gholamin, Teresa F Reyes, Rui Li, Frank Kuhnert, Xiaoyuan Han, Jenny Yuan, Shin-Heng Chiou, Ari D Brettman, Lauren Daly, David C Corney, Samuel H Cheshier, Linda D Shortliffe, Xiwei Wu, Michael Snyder, Pak Chan, Rona G Giffard, Howard Y Chang, Katrin Andreasson, Calvin J Kuo
Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28287163/immunofluorescence-identifies-distinct-subsets-of-endothelial-cells-in-the-human-liver
#18
Otto Strauss, Anthony Phillips, Katya Ruggiero, Adam Bartlett, P Rod Dunbar
As well as systemic vascular endothelial cells, the liver has specialised sinusoidal endothelial cells (LSEC). LSEC dysfunction has been documented in many diseased states yet their phenotype in normal human liver has not been comprehensively assessed. Our aim was to improve characterisation of subsets of endothelial cells and associated pericytes in the human liver. Immunofluorescence microscopy was performed on normal human liver tissue samples to assess endothelial and structural proteins in a minimum of three donors...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28242004/expression-of-toll-like-receptors-2-4-and-6-in-different-cell-populations-of-the-equine-endometrium
#19
Sandra Schöniger, Hilke Gräfe, Heinz-Adolf Schoon
Subfertility in mares is mainly caused by endometrial diseases. Alterations of Toll-like receptors (TLRs) are associated with endometrial disorders in women. This study investigated TLRs 2, 4 and 6 in the equine endometrium. Endometria of 21 mares were examined by histology, PCR and immunohistochemistry. Tissues from 2 mares were considered normal. The remaining showed endometritis, endometrosis and/or angiosclerosis. TLRs 2, 4 and 6 were expressed as transcripts and proteins in all endometria. Immunohistochemistry detected TLRs 2, 4 and 6 in mast cells, luminal and glandular epithelial cells, stromal cells, endothelia, vascular smooth muscle and/or inflammatory cells...
March 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28220498/the-role-of-apical-cell-cell-junctions-and-associated-cytoskeleton-in-mechanotransduction
#20
REVIEW
Sophie Sluysmans, Ekaterina Vasileva, Domenica Spadaro, Jimit Shah, Florian Rouaud, Sandra Citi
Tissues of multicellular organisms are characterised by several types of specialised cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions (AJ) play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signalling. The machineries which functionally connect tight and AJ to the cytoskeleton comprise proteins which either bind directly to cytoskeletal filaments, or function as adaptors for regulators of the assembly and function of the cytoskeleton...
April 2017: Biology of the Cell
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