Is it advisable to go back from bedside to the bench? During the last decade, few topics encountered such a broad interest in bio- gy and medicine as angiogenesis. The amazing ability of the body to restore blood flow by induction of blood vessel growth as part of an adaptive process has alarmed physicians dealing with diseases in which angiogenesis is either exaggerated (as in tumors) or too slow (as in ischemic diseases of heart and brain). Not surprisingly, pro- and antiangiogenic strategies have found their way into clinical trials. For instance, for the USA, the NIH website in early 2004 displayed 38 clinical studies involving either pro- or antiangiogenic th- apies. Given the expected overwhelming wealth of clinical data, the question may be asked whether further exploration of biological mechanisms is required or whether results from the bedside are instructive enough to proceed. This question depends also on the progress of pro- and antiangiogenic clinical trials. In the following, I give a short overview about some of the progress that has been made in this field. Since Judah Folkman proposed antiangiogenic tumor therapy thirty years ago, it has become increasingly evident that agents which interfere with blood vessel formation also block tumor progression. Accordingly, antiangiogenic therapy has gained much attention as a potential adjunct to conventional c- cer therapy.

This reference work presents the basic principles of angiogenesis induction, including the roles of signaling factors such as hypoxia-inducible factors, biophysical stimulation and angiogenic cells. The book also covers lymphogenesis induction. Both the established fundamentals in the field as well as new trends in the vascularization of engineered tissues are discussed. These include pre-vascularization strategies using preparation of channeled scaffolds and preparation of decellularized blood vessel trees, approaches to inducing formation of microvasculature and approaches to inducing the growth of vascular networks. The authors expand on these concepts with current studies of dual-level approaches to engineer vascularized tissue composites. The book concludes with a discussion of current clinical approaches and the use of vascular grafts in the context of providing clinical practice with new tissue engineering strategies.

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

The placenta is an organ that connects the developing fetus to the uterine wall, thereby allowing nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. Proper vascular development in the placenta is fundamental to ensuring a healthy fetus and successful pregnancy. This book provides an up-to-date summary and synthesis of knowledge regarding placental vascular biology and discusses the relevance of this vascular bed to the functions of the human placenta.

The purpose of this book is to highlight novel advances in the field and to incentivize scientists from a variety of fields to pursue angiogenesis as a research avenue. Blood vessel formation and maturation to capillaries, arteries, or veins is a fascinating area which can appeal to multiple scientists, students, and professors alike. Angiogenesis is relevant to medicine, engineering, pharmacology, and pathology and to the many patients suffering from blood vessel diseases and cancer, among others. We are hoping that this book will become a source of inspiration and novel ideas for all.

The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups. The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues. The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation. While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues. With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.

Cell Cycle in the Central Nervous System overviews the changes in cell cycle as they relate to prenatal and post natal brain development, progression to neurological disease or tumor formation.Topics covered range from the cell cycle during the prenatal development of the mammalian central nervous system to future directions in postnatal neurogenesis through gene transfer, electrical stimulation, and stem cell introduction. Additional chapters examine the postnatal development of neurons and glia, the regulation of cell cycle in glia, and how that regulation may fail in pretumor conditions or following a nonneoplastic CNS response to injury. Highlights include treatments of the effects of deep brain stimulation on brain development and repair; the connection between the electrophysiological properties of neuroglia, cell cycle, and tumor progression; and the varied immunological responses and their regulation by cell cycle.

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

Tumor Vascularization discusses the different types of growth of tumor blood vessels and their implications on research and healthcare. The book is divided into three parts: the first one, General Mechanisms, discusses different vessel growth mechanisms, such as sprouting angiogenesis, non-angiogenesis dependent growth, intussusceptive microvascular growth, vascular co-option and vasculogenic mimicry. The second and third parts, entitled Clinical Implications and Therapeutic Implications are dedicated to translating recent findings in this field to patient treatment and healthcare. This book is a valuable source for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in tumor progression and blood vessels.

Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.