Foreword II

The present compilation of articles on the topic of Microvascular Research is both the most comprehensive and most current of the works ever written on this subject. Its breadth is dazzling and the assembled cast of contributors is a Who's Who of the field's best minds. There is virtually no area of scientific discovery relevant to the structure, function and pathology of the microvasculature that is not addressed in this text. Together Drs Shepro and D'Amore have logged more that 75 years of research in vascular biology and their knowledge of the field and of the top scientists in this field is unparalleled.

The volume starts with the basic biology of the cells that comprise the microvascular bed and moves from there to vascular development and permeability, in vivo models, peri-vascular transport and on to the role of the microvascu-lature in specific organ beds as well as in human disease. What is noticeable is the extremely large list of human diseases that are caused or influenced by alterations in the microvasculature. One begins to think that the list of diseases that are not influenced by microvascular alterations must be considerable shorter. Of course, a large amount of the research on microvessels over the past 35 years has been conducted on the topic of tumor angiogenesis and this topic is well covered in this volume.

It is remarkable to see how much progress has been made in microvascular research over the past few years and how much information is now known. In some cases, the text reveals new progress on topics that have been studied for decades. Among these are the relationship of the endothe-lium with the extracellular matrix, endothelial metabolism, endothelial heterogeneity, the distinction between developmental vessel formation and pathologic vessel formation, the traditional experimental models such as the chick chorioallantoic membrane and hamster cheek pouch, the maintenance of vascular tone and the regulation of microvascular hemodynamics, a long-term interest of Dr. Shepro.

At the same time, there are a variety of new areas of microvascular research that have burst onto the scene in just the last few years and these, too, are wonderfully represented in this volume. Among these are the role of ephrins as signaling mediators in vascular cells, the ability of zebrafish to function as model system for vascular biology, the effect of mechanical signals on microvascular structure and function, and the extraordinary new work on VEGF and VEGF antagonists that is leading to important new treatments for both cancer and for vascular diseases of the eye.

If there is a message that emanates from this book as a whole, it is the concept that blood vessels have a crucial yet differing role in the function of virtually every tissue and in the pathogenesis of a host of diseases. No longer is it sufficient to consider blood vessels as passive tubes that merely carry nutrients to tissues. Rather the microvessels are a vital part of every tissue that interact mechanically, biochemically and metabolically with the parenchymal cells of the tissues they support. The communication is elaborate and goes in both directions, from the vessels to tissue and vice versa. If you study the vasculature, you must look at it from the context of the tissue in which it occurs. If you study any specific tissue, you must understand its relationship with the microvessels that inhabit it. Reading this volume allows a new appreciation of these interactions.

It should be noted that Dr. D'Amore began her career as a graduate student in Dr. Shepro's laboratory and is now one of the leading investigators in the field of vascular biology. Perhaps they didn't realize at the time that they would one day put together a volume as definitive and thoughtful as this one. One only hopes that there is a graduate student in Dr. D'Amore's laboratory who can be counted on to update this volume in ten or twenty years.

Bruce Zetter, Ph.D.

Charles Nowiszewski Professor of Cancer Biology

Children's Hospital Harvard Medical School Boston, Massachusetts

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