The fact that ischemic heart disease is the leading cause of morbidity and mortality in the industrial world highlights the importance of the coronary vasculature. This proposal considers the importance of coronary vessel growth as essential, not only during early development, but also in the adult heart faced with various stresses, e.g. hypertrophy, ischemia, hypoxia and chronic exercise. Moreover, the recent exponential increase in studies on therapeutic angiogenesis, many of which are conflicting, suggests that we need to develop a sound understanding of the factors and mechanisms that govern coronary vessel formation. However, existing compilations of these data remain limited to books focusing on specific areas of the coronary vasculature. Thus, there is no single comprehensive work that brings these individual topics together. As a scientist who has conducted research and written reviews addressing many of the areas of coronary vessel research, the PI has the unique background necessary to bring these topics together into a comprehensive monograph. The overall goal of this application is to write a monograph that considers the hierarchy of the coronary vasculature from its embryonic origins through its postnatal growth, adulthood and senescence. This critical review will consider the coronary vasculature with regard to its 1) normal development, 2) anomalies and their possible underlying developmental errors, 3) adaptations to stress (e.g. hypertension, hypoxia and ischemia), and 4) aging. The monograph will be timely because novel technologies have enabled the discovery of molecular mechanisms underlying the assembly and growth of the coronary vasculature and adaptations and alterations that occur in the adult. In addition to utilizing the existing literature, data from archives on human embryos and on models of experimental animals will be incorporated. The book will explore and critically analyze the literature and relate data from experimental animals to the human condition. Images will be included in the book and an expanded version will be on-line. By integrating these areas, clinicians and basic scientists may gain important insights into the interrelationships between different areas of coronary vascular biology. The monograph is intended for at least three groups. First, a major target audience is comprised of all scientists, postdoctoral fellows and graduate students who are in any of the areas of coronary vascular biology. For this audience, the monograph should serve as both a key reference and a source for broadening their understanding of the diversity of the vascular biology field. A second targeted group consists of vascular biologists whose primary interest is in mechanisms of vascular development, in general, and those individuals whose interest is in the vascularization of organs other than the heart. The third targeted group is clinicians who should find the monograph to be a beneficial reference source and overview.
The monograph developed in this project will serve at least three groups of individuals in the health care community. These include cardiologists, coronary vascular scientists and scientists who focus on organs other than the heart. By addressing coronary 1) vascular development, 2) anomalies and 3) therapeutic interventions book will bring together key concepts that will provide the insights that directly relate to cardiovascular medicine. This comprehensive work is significant in that it links basic science and medicine.