PREFACE It is customary, though unnecessary, to preface a volume such as this by highlighting the burden of cardiovascular disease. Suffice it to say that the majority of this volume’s readers (and contributors) will develop some form of cardiovascular disease during their lifetime. I look forward to a time when publications such as this will be of historic interest only and intend to live to see it, if possible. The ongoing battle against cardiovascular disease should not detract from the huge successes made in the last century. We now understand more about the causes of cardiovascular disease than could have been imagined a few decades ago. With this has come a range of diagnostics and treatments that have radically improved our ability to identify, treat, or prevent such diseases. However, there is no room for complacency; every hospital bed contains an example of our failure to fully understand and address why people get sick. The influence of the genome and its regulation on cardiovascular disease has long been suspected. On occasion, debate has ensued regarding the relative contributions of heritability versus environmental and societal factors to an individual’s risk of developing cardiovascular disease. My personal view is that no real distinction between such pressures exists; at some level every element of human life is determined by the sum total of the genomes of many millions of individuals, including those of previous generations. What I’m trying to say is that, basically, it’s all about the genes. The futility of attempting to comprehensively cover the genetics of cardiovascular disease is obvious, and I have made no such attempt. However, this volume assembles a range of reviews that present accessible yet comprehensive descriptions of areas of current interest in cardiovascular science. Each would educate and inform all but experts in the respective areas; I have certainly learnt a great deal editing them. Chapter 1 by Sheila Francis is extremely timely, coming at a time when some angst is being voiced about whether the ubiquitous mouse models of atherosclerosis are sufficiently informative about human disease. It remains to be seen which way the field will go, and it is to be hoped that the difficult decisions faced by research funders will be the right ones. Chapter 2 by Bill Chaudhry and Deborah Henderson presents a summary of the genetics of mammalian cardiac development. The field of developmental biology (formerly embryology) has been rejuvenated by the xi

xii

Preface

prospect that developmental processes underpin many, if not most, diseases; and that recapitulation of such phenomena by “regenerative medicine” holds the prospect of a truly novel approach to treating disease. We will know in the next two decades whether this prospect will flourish or founder. Chapter 3 by Alex Rothman, myself, and Allan Lawrie presents a study of the contribution of microRNA to pulmonary vascular disease. The focus on a rare though devastating disease should not prevent this chapter being of interest to all cardiovascular researchers, since the importance of microRNAs and the promise of therapeutic manipulation extend to all areas of human disease. The paradigm shift provoked by the discovery of microRNAs only a few years ago has already led to plausible strategies for treatment of cardiovascular disease, and it is my prediction that patients with cardiovascular diseases will be treated by these approaches before this volume is entirely outdated. Chapters 4 and 5 highlight a new player in the field of cardiovascular genetics and a pet shop favorite, the zebrafish. Robert Wilkinson, Chris Jopling, and Fredericus van Eeden present in Chapter 4 a summary of the use of zebrafish to model cardiac disease, while in Chapter 5 Wilkinson and van Eeden outline how the same humble organism can be used to understand vascular development and disease. The advantages of this model have led to fundamental breakthroughs in our understanding of cardiovascular development. Scientists less familiar with the system are encouraged to consider how it could be applied to their own areas of interest. Chapter 6 by Mark Thomas and Robert Storey describes the cuttingedge interface between genetics and the response to antiplatelet drugs, one of the hugely successful therapies alluded to above. I will allow myself another prediction that the next decade will see a move toward more personalized drug prescription and that antiplatelet therapy, with both clear benefits and significant risks, will be in the vanguard of this approach. Chapter 7 by Peter Novodvorsky and myself describes the transcription factor KLF2 and its contribution to vascular development and disease. Another major success story, the HMG-CoA reductase inhibitors (statins) may owe some of their success to this molecule, and approaches to manipulate KLF2 might lead to significant benefits for a range of cardiovascular diseases. Until my involvement in this volume I had not fully understood why prefaces contained expressions of gratitude; I now realize these are veiled apologies. With this in mind, I would like to thank Mary-Ann Zimmerman, Helene Kabes, and the production team at Elsevier for their patience and

Preface

xiii

hard work. I would also like to thank the contributors; where this volume succeeds, it is by their efforts. The responsibility for any deficiencies is mine alone. TIMOTHY J.A. CHICO Sheffield, UK