Endothelial Luminal Membrane Glycocalyx

This book focuses on the structural, biochemical, and diverse functional properties of the endothelial luminal membrane glycocalyx (ELMG), an organelle which constitutes the endothelial cell "membrane." It is intended to provide the newcomer with a broad, basic, and brief perspective of the luminal endothelial vascular membrane, and for the more established investigator, a basic overview and integrated perspective of the "universe" we explore. The endothelium is an assortment of heterogeneous regulatory cells whose cytoplasm and cell membranes are joined, forming functional units. There is a tremendous amount of literature on the endothelial cell, constituting seemingly isolated and distinct fields of encapsulated research. However, the multifunctional properties of some molecules give rise to an overlap of findings, frequently ignored between the different fields. The book is divided into three parts. The first part concentrates on the structure of the ELMG, with emphasis on morphological and biochemical composition. The importance of the chemical composition to the physiological functions of the ELMG, such as sieving properties, pharmacology, and flow sensing, is the focus of the second part of the book. Finally, some of the pathologies associated with ELMG dysfunction are explored in the last section. The aim is to provide basic and well-established knowledge in the various individual fields, identify the current concepts in each area, and discuss their respective strengths and weaknesses (including hidden problems). Finally, the overall goal is to integrate areas where overlap is clearly indicated, bringing them all together to provide the first ever basic, integrative, panoramic bird’s-eye view of the field.

Written by internationally recognized leaders in Heparanase biology, the book’s eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.

The world's most renowned researchers in fluid management explain what you should know when providing infusion fluids to surgical patients.

This book introduces the latest research in molecular, cellular, and tissue engineering of the vascular system. Topics covered include the roles of endothelial surface glycocalyx as a mechano-sensor and transducer for blood flow, a barrier to water and solute transport across the vascular wall and to the interaction between circulating cells and the vessel wall, the roles of nuclear envelope proteins and nuclear lamina in regulating vascular functions under blood flow-induced forces, and the roles of smooth muscle cells and extracellular components in arterial vasoconstriction. Other topics covered include non-surgical vascular interventions for coronary artery diseases, genesis and mechanisms of atherosclerotic plaque microcalcifications and human abdominal aortic aneurysms, experiments and modelling for red blood cell and tumor cell movement in microcirculation, transport across the blood-brain barrier and its role in Alzheimer’s disease, mathematical models for cell survival after hyperthermia, application of hypothermia in enhancing treatment for brain and spinal cord injuries, and damage of eardrums due to blast waves. This is an ideal book for biomedical engineers and researchers, medical researchers, and students in biomedical engineering and medical sciences.

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

The endothelium enables communication between blood and tissues and is actively involved in cardiovascular homeostasis. Endothelial dysfunction has been recognized as an early step in the development of cardiovascular diseases: respectively, endothelium represents a potential therapeutic niche with multiple targets. The purpose of the book is to point out some recent findings of endothelial physiology and pathophysiology emphasizing various aspects of endothelial dysfunction connected to the body's internal and external environment. While basic features of the endothelium are presented in an introductory chapter, the authors of the following 17 chapters have provided extensive insight into some selected topics of endothelial (dys)function. The book would hopefully be useful for anyone interested in recapitulating endothelial (patho)physiology and expanding knowledge of molecular mechanisms involved in endothelial dysfunction, relevant also for further clinical investigations.

The partition of fluid between the vascular and interstitial compartments is regulated by forces (hydrostatic and oncotic) operating across the microvascular walls and the surface areas of permeable structures comprising the endothelial barrier to fluid and solute exchange, as well as within the extracellular matrix and lymphatics. In addition to its role in the regulation of vascular volume, transcapillary fluid filtration also allows for continuous turnover of water bathing tissue cells, providing the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic byproducts. Transendothelial volume flow has also been shown to influence vascular smooth muscle tone in arterioles, hydraulic conductivity in capillaries, and neutrophil transmigration across postcapillary venules, while the flow of this filtrate through the interstitial spaces functions to modify the activities of parenchymal, resident tissue, and metastasizing tumor cells. Likewise, the flow of lymph, which is driven by capillary filtration, is important for the transport of immune and tumor cells, antigen delivery to lymph nodes, and for return of filtered fluid and extravasated proteins to the blood. Given this background, the aims of this treatise are to summarize our current understanding of the factors involved in the regulation of transcapillary fluid movement, how fluid movements across the endothelial barrier and through the interstitium and lymphatic vessels influence cell function and behavior, and the pathophysiology of edema formation. Table of Contents: Fluid Movement Across the Endothelial Barrier / The Interstitium / The Lymphatic Vasculature / Pathophysiology of Edema Formation

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