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Author: Evgenia Gerasimovskaya Publisher: Springer Science & Business Media ISBN: 9048134358 Category : Science Languages : en Pages : 240
Book Description
Extracellular purines and pyrimidines (ATP, ADP, UTP and adenosine) are released into the extracellular milieu in response to a variety of stress conditions and act as important regulators of vascular homeostasis. This new book is uniquely focused on the signaling actions of extracellular purines in endothelial cells and the crucial role of extracellular purines in regulation of angiogenesis, vascular tone, cell permeability, wound healing, inflammation and cell-to-cell communication. This book examines the responses of endothelial cells, originating from various tissues (such as cornea, pancreas and uterus), to extracellular nucleotides and adenosine under physiological and pathological conditions, i.e. pregnancy, hypoxia, hypertension, inflammation and diabetes. In the book’s 12 chapters, the role of purinergic signaling in endothelium-dependent tissue perfusion, regulation of endothelial barrier function, and angiogenesis are discussed. The mechanisms of ATP release and its role in intercellular communication are also presented. In addition, the book provides the most up to date mechanisms of extracellular nucleotide metabolism by purine-converting ecto-enzymes and their contribution to purinergic signaling in endothelial cells originating from various vascular beds. This book is a valuable resource for biomedical research scientists, clinical scientists, graduate students and health science professionals interested in the mechanisms of extracellular purine function in endothelial cells under physiologic and pathologic conditions.
Author: Evgenia Gerasimovskaya Publisher: Springer Science & Business Media ISBN: 9048134358 Category : Science Languages : en Pages : 240
Book Description
Extracellular purines and pyrimidines (ATP, ADP, UTP and adenosine) are released into the extracellular milieu in response to a variety of stress conditions and act as important regulators of vascular homeostasis. This new book is uniquely focused on the signaling actions of extracellular purines in endothelial cells and the crucial role of extracellular purines in regulation of angiogenesis, vascular tone, cell permeability, wound healing, inflammation and cell-to-cell communication. This book examines the responses of endothelial cells, originating from various tissues (such as cornea, pancreas and uterus), to extracellular nucleotides and adenosine under physiological and pathological conditions, i.e. pregnancy, hypoxia, hypertension, inflammation and diabetes. In the book’s 12 chapters, the role of purinergic signaling in endothelium-dependent tissue perfusion, regulation of endothelial barrier function, and angiogenesis are discussed. The mechanisms of ATP release and its role in intercellular communication are also presented. In addition, the book provides the most up to date mechanisms of extracellular nucleotide metabolism by purine-converting ecto-enzymes and their contribution to purinergic signaling in endothelial cells originating from various vascular beds. This book is a valuable resource for biomedical research scientists, clinical scientists, graduate students and health science professionals interested in the mechanisms of extracellular purine function in endothelial cells under physiologic and pathologic conditions.
Author: John W. Phillis Publisher: CRC Press ISBN: 9780849369285 Category : Science Languages : en Pages : 460
Book Description
This book provides valuable information for investigators interested in the signaling and regulatory functions of adenosine and the adenine nucleotides. Topics covered in this comprehensive volume include the historical development of research on adenosine and adenosine triphosphate; various aspects of the formation, metabolism, release, transport, and receptors for endogenous adenosine and the adenosine triphosphate; functions of purines at the cellular level; the role of adenosine in the regulation of flow in different vascular beds; and angiogenesis. The book also addresses the purinergic regulation of the cardiac, renal, gastro-intestinal, and central nervous system, as well as potential therapeutic avenues for purine use. The book will be valuable to physiologists, pharmacologists, and other basic and clinical scientists interested in updating their knowledge of the expanding biological roles of these substances.
Author: Do-Geun Kim Publisher: ISBN: Category : Languages : en Pages : 530
Book Description
The brain is the center of cognitive function and also regulates the physiology of the body. Due to its importance, it requires special vascular structure which separates itself from the peripheral circulation to maintain its electrical physiology and protect from insult from circulation. The vasculature of the brain is lined with a single layer of endothelial cells which is sealed with adherent and tight junction molecules. The endothelial cell lining is further insulated with pericytes and astrocytic endfeet. Also endothelial cells express varieties of transporters which selectively allow the entrance of molecules into the brain. This physicochemical vascular entity is called the blood brain barrier. This structural barrier is, however, detrimental in the delivery of molecules to the brain. Many of drugs are dropped out from the pipelines because they cannot show the expected effect in the brain. To overcome this, many approaches were devised to increase the drug delivery to the brain, they were either invasive or ineffective. In previous study, we have shown that adenosine receptor signaling can increase the permeability of large molecules to the brain. Adenosine receptor is the G-protein coupled receptor which is involved in numerous physiological reactions. Activation of adenosine receptor showed potent and reversible increased permeability to the large molecules. In this dissertation, we aimed to reveal if activation of adenosine receptor signaling can increase the permeability in the human primary brain endothelial cell monolayer. Indeed we observed robust and reversible permeability increase in human brain endothelial cells. This was mediated by increased Rho-GTPase activity and following stress fiber formation which subsequently disrupted the tight and adherens junctional molecules. Activation of AR also increased the permeability to chemotherapeutics Gemcitabine. Also, we studied if adenosine receptor signaling can increase transcellular pathway which is mainly mediated by transporters highly expressed on the brain endothelial cells, especially P-glycoprotein. Indeed we observed that AR activation can increase the accumulation of the P-glycoprotein substrate in human primary brain endothelial cells by down regulating the expression and function of P-glycoprotein. Also, we could observe that it down-regulates the P-glycoprotein and thereby increase the accumulation of epirubicin, a P-glycoprotein substrate, in the brain of the mouse. Collectively, we showed that AR activation can increase the permeability paracellular permeability of the human primary brain endothelial cells and also down regulate the P-glycoprotein function and enhance the transcellular permeability. These dual mechanism of regulating the permeability of the blood brain barrier might be beneficial in drug delivery in the brain which will benefit millions of patients suffering from the neurodegenerative disease or brain cancers.
Author: Michitoshi Inoue Publisher: Springer Science & Business Media ISBN: 4431683674 Category : Medical Languages : en Pages : 330
Book Description
Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.
Author: Michel Félétou Publisher: Morgan & Claypool Publishers ISBN: 1615041230 Category : Science Languages : en Pages : 309
Book Description
The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
Author: D. Neil Granger Publisher: Morgan & Claypool Publishers ISBN: 1615041656 Category : Medical Languages : en Pages : 99
Book Description
The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References
Author: Gyorgy Hasko Publisher: CRC Press ISBN: 1420005774 Category : Medical Languages : en Pages : 377
Book Description
After a century of research, several lines of evidence now indicate that the ability of adenosine to directly control inflammatory cells has a major impact on the functions of the inflammatory and immune systems. Consequently, many promising therapeutic approaches are beginning to emerge that focus on the modulation of adenosine, including the deve
Author: Sarah Y. Yuan Publisher: Biota Publishing ISBN: 1615041214 Category : Medical Languages : en Pages : 160
Book 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.