Endothelial Cytoskeleton

Author by : Juan A. Rosado
Languange : en
Publisher by : CRC Press
Format Available : PDF, ePub, Mobi
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Description : This book presents a concise synthesis of the current knowledge and recent advances in the structure, organization and functional role of the cytoskeleton in endothelial cells. Particular attention has been given to the different features of the regulation of vascular function mediated by the endothelium. Since cytoskeleton is a scaffolding element that regulates the architecture of the cell and additionally controls several fundamental aspects of intracellular signaling, this book will serve as a comprehensive resource for those interested in these fascinating biological processes associated with vascular biology. The book has been divided into two major sections: general aspects of the endothelial cytoskeleton and the role of the role of the endothelial cytoskeleton in different functions of the vascular wall.


Real Time Monitoring And Quantification Of Drug Induced Changes In Endothelial Cytoskeleton Filaments Using A Cellular Impedance Biosensor

Author by : Anonim
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 61
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File Size : 41,8 Mb
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Description : The analysis of electrical signals originating from biological cells and tissues have yielded a large amount of useful information over the past years. Technologies have been developed, wherein we can monitor the health of the biological material of interest using these electrical signals. Instruments for the study of living cells have historically been of significant importance for such things as basic neuroscience, cell biology, pharmaceutical screening, environmental monitoring, and toxin detection. One of the practical realizations of these methods was successfully implemented by Giaver and Keese with their Electric Cell-Substrate Impedance Sensing (ECIS) system. The purpose of this Masters Thesis is to showcase the use of a Cellular Impedance Biosensor setup based on the ECIS system in real-time monitoring of endothelial barrier function and quantify the dynamic changes of the cytoskeleton filaments induced by different drugs. The filaments of the endothelial cell cytoskeleton play a critical role in cellular micro motion and the inflammatory response. The fact that the cellular cytoskeleton is the essential force behind all the motile activities of the cell is used in drug discovery methods to design ways so as to kill tumor cells and developing cell-based therapies for different cardiovascular pathologies. Cytochalasin D was chosen to study the actin filament response as the drug specifically inhibits the polymerization of actin filaments, which play a crucial role in the cellular mechanical strength and micromotion. Nocodazole was chosen to study microtubules, which play a pivotal part in the cellular mitotic activities and locomotion. These drugs were chosen as they have extreme effects on the cytoskeleton and would be ideal to showcase the use of the biosensor in tracking the intracellular dynamics. The biosensor system provides a simple interface for monitoring the electrical activity and impedance characteristics of populations of cultured cells over extended periods. The cell - sensor interface is created as cells attach to the gold electrode surface pre-coated with fibronectin. Using these impedance measurement techniques based on a simple cellular geometric model, we have been able to successfully monitor cellular adhesion, motility, proliferation and changes in the cellular cytoskeleton induced by different drugs as mentioned above. The kinetic response of the cellular cytoskeleton to different doses of these drugs is translated as changes in the impedance measured by the biosensor setup. The data obtained from the setup were quantified by correlating them with the images obtained by confocal microscopy. A wavelet transformation algorithm is applied to the acquired data in an attempt to capture the fluctuations and compare the cellular behavior before and after the addition of drugs. Study of the disruption of these filaments by toxins and pharmacological agents holds lot of promise to provide a model for studying their role in endothelial cell biomechanics and the pathology of cardiovascular, pulmonary, and renal disease. This thesis presents a cellular impedance biosensor setup that can carry out this study in real time with high sensitivity and reproducibility. Using these impedance measurement techniques, we have been able to successfully monitor cellular adhesion, motility, proliferation of different type of cells and their response to external stimuli.


Regulation Of Endothelial Barrier Function

Author by : Sarah Y. Yuan
Languange : en
Publisher by : Morgan & Claypool Publishers
Format Available : PDF, ePub, Mobi
Total Read : 72
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Description : The vascular endothelium lining the inner surface of blood vessels serves as the first interface for circulating blood components to interact with cells of the vascular wall and surrounding extravascular tissues. In addition to regulating blood delivery and perfusion, a major function of vascular endothelia, especially those in exchange microvessels (capillaries and postcapillary venules), is to provide a semipermeable barrier that controls blood-tissue exchange of fluids, nutrients, and metabolic wastes while preventing pathogens or harmful materials in the circulation from entering into tissues. During host defense against infection or tissue injury, endothelial barrier dysfunction occurs as a consequence as well as cause of inflammatory responses. Plasma leakage disturbs fluid homeostasis and impairs tissue oxygenation, a pathophysiological process contributing to multiple organ dysfunction associated with trauma, infection, metabolic disorder, and other forms of disease. In this book, we provide an updated overview of microvascular endothelial barrier structure and function in health and disease. The discussion is initiated with the basic physiological principles of fluid and solute transport across microvascular endothelium, followed by detailed information on endothelial cell-cell and cell-matrix interactions and the experimental techniques that are employed to measure endothelial permeability. Further discussion focuses on the signaling and molecular mechanisms of endothelial barrier responses to various stimulations or drugs, as well as their relevance to several common clinical conditions. Taken together, this book provides a comprehensive analysis of microvascular endothelial cell and molecular pathophysiology. Such information will assist scientists and clinicians in advanced basic and clinical research for improved health care. Table of Contents: Acknowledgments / Introduction / Structure and Function of Exchange Microvessels / Methods for Measuring Permeability / The Endothelial Barrier / Signaling Mechanisms in the Regulation of Endothelial Permeability / Endothelial Barrier Protectors / Pathophysiology and Clinical Relevance / Conclusion / References


The Actin Cytoskeleton In Cell Motility Cancer And Infection

Author by : Joel Pardee
Languange : en
Publisher by : Morgan & Claypool Publishers
Format Available : PDF, ePub, Mobi
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Description : The cell is no longer considered to be a bag full of enzymes dissolved in a liquid cytoplasm. It is now known that the cytoplasm is an exquisitely ordered structure of properly placed organelles and enzyme complexes that are suspended from an intricate network of structural protein polymers termed the cytoskeleton. All movement of organelles and vesicles within the cell is regulated by this cytoskeleton, and it is clear that the cytoskeleton is responsible for all of the cell's external movement as well. In this lecture, we will consider how the cytoskeleton elicits cell migration.The three main elements of the cytoskeleton are microtubules, intermediate filaments, and actin filaments. Microtubules are essential for (a) intracellular transport within the cytoplasm and transport between the nucleus and cytoplasm, (b) the structure and movement of all cilia and flagella, and (c) the structure of the mitotic spindle and movement of chromosomes on the spindle during cell division. Intermediate filaments give structural integrity to virtually all cells and tissues by providing an intracellular network of flexible cables that strengthen internal cell structure and stabilize cell-to-cell adhesion. It is this intercellular binding property that stably joins epithelial cells together to provide the protective functions of skin and the integrity of the intestinal mucosa.Actin is a highly conserved protein ubiquitous to all eukaryotic cells. Actin is absolutely required for (a) cell migration, (b) the contraction of muscle (both striated and smooth), (c) the structure and function of many cell protrusions (e.g., microvilli, filopodia, lamellopodia, blood platelet projections), (d) division of the cytoplasm (cytokinesis) during telophase of cell mitosis, and (e) movement and placement of organelles within the cell. Actin filaments are also called thin filaments because of their very slender (70 Ã…) diameter.


Endothelial Cell Dysfunctions

Author by : M. Simionescu
Languange : en
Publisher by : Springer Science & Business Media
Format Available : PDF, ePub, Mobi
Total Read : 62
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Description : Noted experts survey and evaluate the latest research in the growing field of endothelial cell involvement in the initiation and development of various diseases. Research-oriented chapters span a diversity of topics, including endothelial cell response to various injuries and its crucial role in inflammation, immunity, viral infection, hypertension, hyperlipidemia, atherosclerosis, diabetes mellitus, neoplasia, and metastasis.


Tumor Angiogenesis

Author by : Dieter Marmé
Languange : en
Publisher by : Springer Science & Business Media
Format Available : PDF, ePub, Mobi
Total Read : 71
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Description : Tumor angiogenesis is one of the most prominent mechanisms driving tumor development and progression. This book is written by internationally renowned experts. Part 1 describes the basic mechanisms. Tumor-angiogenic signaling pathways are presented as new potential targets for anti-angiogenic therapy. Part 2 reviews the efforts made to validate new targets and to show efficacy in animals. Part 3 is devoted to the clinical development of the novel anti-angiogenic drugs and their use in clinical practice.


Perspectives On Lung Endothelial Barrier Function

Author by : C.E. Patterson
Languange : en
Publisher by : Elsevier
Format Available : PDF, ePub, Mobi
Total Read : 58
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Description : Covers endothelial biology from the fundamentals of structure and lung fluid balance physiology to descriptions of the molecular mechanisms involved in the development of lung failure. This illustrated text provides the knowledge of endothelial function, vascular integrity, pulmonary function, and pathophysiology in respiratory failure.


Identification Of Fmnl3 As A Novel Regulator Of The Cytoskeleton In Angiogenesis

Author by : Clare L. Hetheridge
Languange : en
Publisher by : Unknown
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Total Read : 39
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Description : Sprouting angiogenesis is the formation of new blood vessels from the pre-existing vasculature. Endothelial cells in quiescent blood vessels form a highly organised array with tight cell-cell junctions and uniform polarity. When pro-angiogenic signals initiate angiogenesis, endothelial, cells must become invasive and migrate into the extracellular matrix that surrounds the blood vessels. Sprouting endothelial cells become highly elongated, and this involves dramatic changes in cell shape and polarity. The mechanisms controlling angiogenic morphogenesis are poorly characterised. Cell shape and polarity are orchestrated by the cytoskeleton. The aim of this study was to characterise the cytoskeleton as endothelial cells convert to an angiogenic morphology, and identify novel regulators of this process. An in vitro model of angiogenesis was used to study endothelial cell elongation, in which endothelial cells form capillary-like tubes. It was found that this process was accompanied by the reorganisation of the microtubule network to form a parallel array along the length of the endothelial cells. These microtubules accumulated a modified form of the tubulin monomer, which indicates microtubule stabilisation. Stabilised microtubules were not found in quiescent endothelial cells, and so were associated with the initiation or maintenance of endothelial cell elongation. The formin family of cytoskeletal regulators have been shown to cause similar stabilisation of the microtubule network, in addition to modulating actin dynamics. A screen of the form in family of proteins in the in vitro model demonstrated that the novel formin FMNL3 is critical for endothelial cell elongation. Loss of FMNL3 caused a dramatic decrease in endothelial cell tube formation and resulted in disorganisation of the microtubule cytoskeleton. This study describes the identification of FMNL3 as a novel cytoskeletal regulator and its characterisation in endothelial cells.


Artery

Author by : Anonim
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 60
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File Size : 45,6 Mb
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Description :


Cytoskeleton And Atp In Sulfur Mustard Mediated Injury To Endothelial Cells And Keratinocytes

Author by : Daniel B. Hinshaw
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 36
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File Size : 44,5 Mb
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Description : The goal of this project has been to define the nature of the cytopathology induced by sulfur mustard (SM) in endothelial cells and keratinocytes which accounts for vesication. Using fluorescence microscopic techniques and biochemical assays we tested the hypotheses that SM injury can cause two forms of cell death in endothelial cells and keratinocytes, apoptosis and necrosis, and that they result in cytoskeletal and morphologic changes which account for SM-induced blister formation. SM induced apoptosis and necrosis in endothelial cells, but only caused necrosis in keratinocytes. Minimal cell death was seen in keratinocytes with


Cytoplasmic Structures Advances In Research And Application 2012 Edition

Author by : Anonim
Languange : en
Publisher by : ScholarlyEditions
Format Available : PDF, ePub, Mobi
Total Read : 28
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File Size : 54,8 Mb
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Description : Cytoplasmic Structures—Advances in Research and Application: 2012 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Cytoplasmic Structures. The editors have built Cytoplasmic Structures—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Cytoplasmic Structures in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Cytoplasmic Structures—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.


The Cytoskeleton And Atp In Sulfur Mustard Medicated Injury To Endothelial Cells And Keratinocytes

Author by : Anonim
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 87
Total Download : 671
File Size : 43,9 Mb
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Description : The major goal of this project is to test the hypothesis that sulfur mustard (SM)-mediated cell death in keratinocytes and endothelial cells is primarily apoptotic in nature, and that several factors (e.g., cellular levels of adenosine triphosphate (ATP), reactive oxygen species ROS) help define this process. Using biochemical and fluorescence microscopic techniques to measure several parameters of cell death over a 72 hour time course of SM injury, we found that keratinocytes develop mixed features of both apoptosis and necrosis, but more slowly than endothelial cells which exhibit a more classical pattern of apoptosis. Caspase-3, a protease which plays a central role in programmed cell death was activated in both cell types by SM. In a model of moderate ATP depletion (approx. 50% of control) endothelial cell progression into apoptosis was suppressed after SM injury followed by later increases in necrosis at higher SM concentrations. Protective effects of N-acetyl-l-cysteine (NAC) on SM-injured endothelial cells were found to be glutathione (GSH)-dependent but other studies assaying for ROS within SM-injured cells were as yet inconclusive. Our results thus far suggest that cell death induced by SM may represent a continuum between the extremes of apoptosis and necrosis. Caspase activation appears to be a critical element common to SM-induced endothelial cell and keratinocyte death and thus may be an important target for therapeutic intervention.


Microvascular Research Biology And Pathology Two Volume Set

Author by : David Shepro
Languange : en
Publisher by : Elsevier
Format Available : PDF, ePub, Mobi
Total Read : 97
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File Size : 53,6 Mb
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Description : The microvasculature refers to the smallest blood vessels, arterial and venous, that nurture the tissues of each organ. Apart from transport, they also contribute to the systematic regulation of the body. In everyday terminology, the microcirculation is "where the action is." Microcirculation is directly involved in such disease states as Alzheimers, inflammation, tumor growth, diabetic retinopathy, and wound healing- plus cardiovascular fitness is directly related to the formation of new capillaries in large muscles. Microvascular Research is the first book devoted exclusively to this vital systemic component of the cardiovascular system and provides up to date mini-reviews of normal functions and clinical states. The contributing authors are senior scientists with international reputation in their given disciplines. This two-volume set is a broad, interdisciplinary work that encompasses basic research and clinical applications equally. * Broad coverage of both basic and clinical aspects of microvasculature research * Contains 167 chapters from over 300 international authors * Each chapter includes key figures and annotated references


Endothelium

Author by : Ayse Basak Engin
Languange : en
Publisher by : CRC Press
Format Available : PDF, ePub, Mobi
Total Read : 23
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Description : The function and life span of endothelial cells have a large impact upon the quality and expectancy of an individual's life. During low perfusion, the adaptation of different cells to hypoxia precipitate the aggressive progression of diseases. Although the clinical studies have convincingly shown that endothelial dysfunction occurs whenever the biological functions or bioavailability of nitric oxide are impaired, in all these scenarios, the role of endothelial cell-destructive process cross-talk is yet poorly understood. This book focuses on the contribution of molecular mechanisms to endothelial dysfunction in related metabolic disorders.


The Cytoskeleton And Atp In Sulfur Mustard Mediated Injury Endothelial Cells And Keratinocytes

Author by : Daniel B. Hinshaw
Languange : en
Publisher by : Unknown
Format Available : PDF, ePub, Mobi
Total Read : 73
Total Download : 503
File Size : 44,6 Mb
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Description : The major goal of this project has been to test the hypothesis that sulfur mustard (SM)-mediated cell death in keratinocytes and endothelial cells is primarily apoptotic in nature, and that several factors (e.g. cellular levels of adenosine triphosphate (ATP), reactive oxygen species ROS, the presence of a nucleus) help define this process. Using biochemical and fluorescence microscopic techniques to measure several parameters of cell death, we found that keratinocytes undergo apoptosis in response to SM, but less synchronously than endothelial cells which exhibit a more classical pattern of apoptosis. Caspase-3, a protease which plays a central role in programmed cell death was activated in both cell types by SM, but more slowly in keratinocytes. In models of ATP depletion, endothelial cell and keratinocyte progression into apoptosis was suppressed after SM injury. Experiments with enucleated cytoplasts demonstrated a nuclear-dependence for at least some aspects of SM-mediated cell death. Protective effects of N-acetyl-1-cysteine (NAC) on SM-injured endothelial cells were found to be glutathione (OSH)-dependent but other studies assaying for ROS within SM-injured cells demonstrated no direct role for ROS in SM-mediated toxicity. We have found that cell death induced by SM is irreversible but development of the apoptotic phenotype may be prevented by inhibition of caspase activation, even after SM exposure. Thus, caspase activation appears to be a critical element common to SM-induced endothelial cell and keratinocyte death, and may be an important target for therapeutic intervention.


The Role Of Microtubules In Endothelial Cell Adaptation To Shear Stress

Author by : Shannon Lee McCue
Languange : en
Publisher by : Unknown
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Total Read : 89
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Description : Shear stress, the fictional force of blood flow, affects the structure of blood vessels, for example, an increase in flow leads to an increase in vessel diameter. Cellular remodeling also occurs in the endothelium; the monolayer of cells that line the inner surface of the vessel wall and are constantly in contact with the blood. In straight areas of vessels where flow is laminar the endothelial cells are elongated but at curves and bifurcations flow is complex. Alterations in blood flow cause the endothelium to morphologically adapt by remodeling the cell-cell and cell-substrate adhesions, and the cytoskeleton. This thesis examined the role of microtubules, a component of the cytoskeleton, in adaptations of vascular endothelium to shear stress. In sheared endothelial cultures, the cells become elongated and aligned in the direction of flow and are polarized. The adhesion complexes and cytoskeleton are reorganized, but how this process occurs is unknown. My results demonstrate that shear stress-induced polarization of the endothelium is via a tightly controlled process that is regulated by microtubule dynamics and the enzyme GSK-3beta. Furthermore, the actin cytoskeleton and the motor protein, kinesin, are critical for endothelial cells to change shape. Microfilaments guide dynamic microtubules to the poles of the cells, and kinesin, associated with stable microtubules, transports intracellular proteins to the cell cortex. Understanding the process of how endothelial cells adapt to alterations in blood flow, will provide important insights into both endothelial cell biology and the general control of cell motility.


Oxidative Stress In Cancer Aids And Neurodegenerative Diseases

Author by : Luc Montagnier
Languange : en
Publisher by : CRC Press
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Total Read : 99
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Description : Based on a conference on Oxidative Stress and Redox Regulation, held at the Pasteur Institute, Paris, this work examines fundamental, chemical, biological and medical studies of free radicals on different targets and the consequences of their reactivity. It covers the chemistry and biochemistry of free radicals, free radicals as second messengers that group the activation of transcription factors and enzymes, the importance of the antioxidant system in cell metabolism regulation, and the role of free radicals and antioxidants in disease management. The editors of this work are three of the most respected pioneers in the field. Dr. Montagnier is credited as the discoverer of HIV.