Endothelial Cytoskeleton

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.

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.

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

This three-volume compendium is the most comprehensive work, to date, on endothelium cells and their important role in the functions of the internal framework. The endothelial cell is broken down into its different properties, taking into consideration its part in metabolic, hemostatic, and immunological processes, as well as their interac-tion with each other and different cell types. Numerous illustrations featured throughout help clarify the importance of endothelium in maintaining the internal status quo. These volumes are indispens-able to researchers, physicians, and others interested in endothe-lium, vascular biology, and circulatory research.

Although blood capillaries were first observed through a flea-lens microscope by Malpighi in 1661,200 more years elapsed before the cellular nature of the vessel wall was conclusively demonstrated. Beginning with the middle of the 19th cen tury, our knowledge of the histological organization of blood vessels has steadily increased. However, the endothelium, which for a long time was considered to be just an inert barrier lining, had been barely explored until three decades ago. Since then, there has been an upsurge of interest in the fine structure and function of endothelial cells. Intense in vivo and in vitro investigations have revealed that the endothelial cell is a key element in a wide variety of normal activities and diseases. A large number of investigators and laboratories have been attracted to endothelial cell research, thus supporting the expansion of the continuously grow ing and diversifying field of endotheliology. The number of articles published annually on this subject has increased from a few score at the beginning of the 1970s to more than a thousand in recent years, and an increasing number of journals, books, societies, and symposia focused primarily on the vascular en dothelium have marked the last decade.

The participation of endothelial cells in various physiologic and pathologic processes has been hypothesized since before the turn of the century. However, until recently, direct evidence for endothelial involvement in these processes has been extremely difficult to obtain due to the inability to study endothelial cell function in vitro. Though the possibility of using cultured endothelial cells to study endothelial cell function in vitro was recognized many years ago, the inability to culture unambiguously identifiable endothelial cells limited investigators in their studies of endothelial function. As a result, the field of endothelial cell biology lay relatively fallow for many years. The development in the early 1970's of routine and easily implemented methods for culturing human endothelial cells and the demonstration that cultured endothelial cells synthesized a physiologically relevant protein, Factor VIII/von Willebrand Factor, quickly changed this state of affairs. Over the following decade the scope of endothelial cell research rapidly widened, spreading in a number of directions. First, methods were developed to culture endothelial cells from a variety of species. Second, methods were developed to culture endothelial cells from different organs and types of blood vessels (arteries, veins, and capillaries) within a single species. Third, and most important, investigators began using cultured endothelial cells as tools to study the potential involvement of endothelial cells in a wide assortment of biologically interesting processes. The net result has been a tremendous increase in our understanding of endothelial cell function.

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.

This book describes the methods of analysis and determination of oxidants and oxidative stress in biological systems. Reviews and protocols on select methods of analysis of ROS, RNS, oxygen, redox status, and oxidative stress in biological systems are described in detail. It is an essential resource for both novices and experts in the field of oxidant and oxidative stress biology.