scope:

Preface

Until the mid 19th century, the endothelium was considered to be little more than an inert layer of nucleated cellophane. In the 1950s and 1960s, the use of physiological assays and electron microscopy provided new insights into the role of the endothelium in inflammation. The development of cell culture techniques to harvest and grow endothelial cells from the human umbilical vein in the 1970s revolutionized the field of endothelial cell biology, leading to breathtaking advances in research and development.

At the same time, there has been a growing awareness that the endothelium displays heterogeneous properties in vivo. Electron microscopy studies in the last century were the first to uncover site-specific differences in endothelial structure and function. Over the past two decades, additional avenues of research have uncovered previously unimaginable levels of complexity in the intact endothelium. It is now recognized that phenotypic heterogeneity is mediated, in large part, by the microenvironment. Thus, the very assay that helped to jumpstart the field of endothelial cell biology-namely, in vitro cell culture-has fallen short in providing insight into the spatial and temporal dynamics of this cell layer. This limitation has been circumvented by the recent development of novel assay systems to interrogate the endothelium in the context of its native environment, either in the living organism or in a reconstituted system in vitro. Such advances are beginning to paint a clearer picture of a cell layer that is teeming with life and every bit as active as other organ systems. When combined with imminent advances in diagnosis (e.g., molecular imaging and proteomics) and therapy (e.g., endothelial cell ''attenuating'' agents), the field of endothelial biomedicine has never looked so promising.

Unfortunately, the exchange of information and ideas among vascular biologists has long been hampered by the existence of infrastructural barriers-intellectual, financial, cultural, and otherwise. Investigators who study endothelial cell biology in vascular beds outside the heart tend to interact with other members of their own organ-specific discipline-for example, blood-brain barrier experts with neuroscientists, pulmonary endothelium investigators with respiratory physiologists, molecular and cell biologists studying endothelium in sickle cell anemia with their hematology and oncology colleagues.

There is little question that a full understanding of the endothelium in health and disease-including its potential as a therapeutic target-will require a more complete synthesis of the field. The purpose of this first edition of Endothelial Cells in Health and Disease is to begin the process of bringing together-for the first time-endothelial cell biologists from different disciplines to summarize recent progress in their respective fields.

The book is divided broadly into five sections. The first section will provide an overview of the endothelium as an organ system followed by a consideration of historically recognized ''specialized'' endothelium, including the blood-brain barrier, lymphatics, and high endothelial venules. The second section highlights new and exciting proteomic and genomic techniques for mapping endothelial cell heterogeneity. The third section is focused on epigenetic and environmental determinants of endothelial cell function, and includes chapters on genetic predetermination, fate mapping studies, oxygen tension, hemodynamics, and vascular bed-specific growth factor signaling. The fourth section covers a subset of phenotypes of the endothelium, including barrier function and leukocyte transmigration. The final section is devoted to a consideration of endothelium in different disease sates, including tumors, sepsis, sinusoidal obstruction syndrome, hypercoagulability, pulmonary hypertension, and transplantation. Additional chapters cover transcriptional networks, endothelial progenitors, circulating endothelial cells and, importantly, a clinician's view of endothelial based-disease.

A book such as this is necessarily limited in size and scope. As a result, several important topics have been excluded from the current edition. Perhaps the most conspicuous of these omissions is a discussion of coronary artery disease. This should not be construed as an oversight or lack of interest on my part. Rather, I have chosen to focus this book on other areas in vascular biology, with the assumption that those readers interested in pursuing the coronary bed have access to a wealth of excellent reviews in the literature.

Many other important areas have been omitted, including a description of endothelium in the retina, the gastrointestinal tract, the skin, and the bone marrow; a consideration of angiogenesis; a summary of novel strategies for diagnosing endothelial-based diseases; and the application of evolutionary principles and complexity theory to an understanding of the endothelium. It is my goal to include these and related topics in subsequent editions of this book.

I would like to thank all the contributors who worked hard to meet the deadlines and produced such excellent chapters. I am indebted to Mitchell Halperin, who gave me the courage to think and speak outside the box, to Bob Rosenberg who introduced me to the wonders of the endothelium, and to Michael Gimbrone who has been a constant source of inspiration.