Endothelial Cell Biology In Health And Disease

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.

In recent years there has been rapid progress in research on vascular endothelium. This has led to significant advances in our understanding of the structure and function of vascular endothelium in health and disease, including such aspects as the permeability of endothelium in relation to its ultrastructural correlates, theoretical basis, regulatory factors, and role in atherogenesis; the interaction between endothelium and blood cells; the endothelial release and processing of a number of important physiological agents, such as eicosanoids, hemostatic factors, and histamine; the cell biology of endothelium with respect to the cytoskeletal apparatus, cell activation, and cell locomotion; and the role of endothelium in microcirculatory regulation in normal and pathophysiological circumstances. A Symposium on "Vascular Endothelium in Health and Disease" was held on August 5-6, 1987, at the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China, following the 4th World Congress for Microcirculation in Japan. Experts working on various aspects of vascular endothelium came from allover the world to participate in this two-day Symposium and gave excellent presentations. This volume, embodying the proceedings of that Symposium, is a collection of the papers given by the speakers with, in many cases, further updating and new information added subsequent to the Symposium. The Institute of Biomedical Sciences (IBMS), the site of this Symposium, is a newlJl established research institution, which has vascular endothelium as one of its areas of research emphasis.

This reference serves as the first source to gather current data from endothelial cell biologists in various disciplines to summarize recent progress in the field-providing a complete understanding of the endothelium in health and disease and demonstrating its potential as a therapeutic target.

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.

We are delighted to offer this textbook to the scientific community, entitled Endothelial Progenitor Cells in Health and Diseases, which covers a timely topic in the rapidly evolving discipline of vascular biology. Written primarily for a life science audience and clinicians, the fundamentals of EPCs biology and the latest characterization and definition in health and diseases are introduced, followed by explanations of the most cutting-edge cell therapy methods to cure ischemic diseases. In Section One, endothelial cell progenitor isolation methods and biological characterization were reported. The discovery of this novel endothelial progenitor cells (EPC) concept has overturned the previous dogma which suggested that vasculogenesis could only occur during embryogenesis. In fact, both vasculogenesis and angiogenesis may potentially have a synergistic role in postnatal revascularization. Also, this chapter summarized recent advances in EPC biology such as biological function, origin, definition, and classification. Each EPC culture and isolation method is clearly defined to prevent confusion in EPC biology. Section Two focuses on EPC biological function alteration in cardiovascular diseases (CVD). Several large clinical trials have reported that the number and biological function are strongly associated with major adverse cardiovascular events. The diagnostic and prognostic potential of EPC is crucial in terms of CVD. In Section Three, biological dysfunction mechanisms of EPC and their scarcity in diabetic patients' peripheral blood were clearly described. Preclinical studies have shown that EPC-based therapy is feasible, safe, and efficacious in multiple disease states. Subsequently, this has led to several clinical trials demonstrating the feasibility and safety profile of EPC therapy against cardiovascular ischemic diseases. In Section Four, regenerative medicine pioneers discussed EPCs translation to the clinic and cell transplantation challenges along with their solutions. Personalized stem cell-based therapy approaches employing several clinical biomarkers, disease-related genetic-trait evaluation methods, and advanced analyses with state-of-the-art computational methods such as machine learning-based prediction can increase cell therapies' efficacy and decrease treatment costs. The last chapter in the book describes a therapeutic application of EPC-derived extracellular vesicles to cure CVD.

Vascular endothelial plays a significant role in regulating blood flow, and endothelial cells (EC) have highly active metabolic functions. This volume focuses on Vascular Endothelium, NO and Hypertension and is a continuum of the volumes on Mechanobiology of Cartilage and Chondrocyte.

Endothelial cell biology has developed into a vibrant discipline and has become a critical instrument to study several disease processes on the cellular and molecular level. It is now widely recognized that dysfunctions of normal endothelial cell homeostasis are involved in some of the most important human diseases, including ischemic heart diseases, hypertension, atherosclerosis, tumors, diabetes, arthritis, and inflammation. Further, the increasing importance and recognition of the field of vascular biology in general requires in vitro and in vivo techniques in order to address the complex questions. Methods in Endothelial Cell Biology is a comprehensive practical "how-to"-guide summarizing the most relevant established techniques as well as a number of new emerging techniques. Easy-to-follow reliable protocols provide a useful lab bench resource for the experienced researcher and newcomer to the field.