Unraveling the Complex Process of Restenosis From Bench to Bedside
Henricus J. Duckers, MD , P h D ,
Caroline Cheng, P h D , Dennie Tempel, BS c, and Patrick W. Serruys, MD , P h D
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INTRODUCTION
The introduction of coronary balloon angioplasty in the late 1970s by Andreas Gruentzig provided an innovative, less invasive method for revascularization of patients with coronary artery disease. This has subsequently led to a rapid development of new percutaneous devices to treat atherosclerotic vasculopathies. Following its success in the initial studies, the expanded use of angioplasty in the clinic has shown that the arteries could react to angioplasty by a proliferative process similar to wound healing, a process known as restenosis. Defined as a renarrowing of the treated vessel area that equals or exceeds 50% of the lumen in the adjacent normal segment of the artery, restenosis severely limited the success of percutaneous coronary intervention. Together with the high prevalence of this vasculopathy, which ranges from 30% to 60% of lesions treated, an intensive search was prompted for interventional techniques that could min- imize the risk of restenosis.
For the last two decades, intervention cardiologists and vascular biologists alike have conducted numerous studies to increase their understanding of its complex mech- anism in order to cope with this new form of proliferative vascular disease. From the outcomes of these studies it has become increasingly clear that the success of any inter- ventional method must be determined, not only by its reliability and efficiency in recov- ering the lumen of the diseased artery, but also by reducing its likelihood in triggering the process of restenosis.
Recently, research, diagnostics, and therapy development in restenosis have hugely advanced, with new insights of the disease emerging rapidly as vascular biologists benefit from innovative laboratory techniques that have emerged from the molecular
From: Contemporary Cardiology: Essentials of Restenosis: For the Interventional Cardiologist Edited by: H. J. Duckers, E. G. Nabel, and P. W. Serruys © Humana Press Inc., Totowa, NJ
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4 Part I / Pathophysiology and Diagnosis
biology, cell biology, and immunology field. The application of these findings has in turn helped to design new treatments for restenosis. In addition to this, rapid advances in the development of diagnostic tools that enable early detection of restenotic lesions, and the emergence and subsequently, large-scale adaptation and refinement of (drug-eluting) stents, has pushed clinical management of this proliferative vascular disease into an inno- vative era, in which restenosis is adequately reduced and the healing of the arterial wall after PCI is optimized.
This book provides the practicing cardiologists and biologists an elaborate review of the current advances in the field. The process of restenosis will be explored from bench to bedside, encompassing in equal detail the newest scientific findings of the biological mechanisms as well as the progression in development of diagnostics and treatments. It also provides the reader with a basic understanding of the biological process and the latest development in diagnostics and treatments of the disease, together with an up-to- date detailed discussion of the most important recent findings. This makes it an excel- lent handbook for introducing the subject to new intervention cardiologists, vascular biologists, and medical students.
It will start by describing the epidemiology and the basic pathogenesis (Part I), supply- ing the necessary background information, and making the reader familiar with the defi- nitions and different aspects of restenosis. It will also include chapters that encompass detailed description of the clinical manifestation and the histomorphological representa- tion of restenosis by well-established investigators who pioneered this particular field.
The mechanisms by which important factors such as shear stress and the immune system drive the pathogenesis of restenosis, are explored by experts in these particular fields. The last chapter of Part I will discuss the different animal models that are commonly used for restenosis research, providing the interested cardiologist–scientist key knowledge about the advantages, drawbacks, and limitations of each arterial injury model.
In Part II, the novel molecular biological mechanisms underlying restenosis will be discussed in depth. The reader will be introduced to the use of genomic and proteomic tools in animal and patient studies. It will provide a clear perspective to the clinical application of these molecular principles in vascular disease. The last chapters focus on the contribution of circulatory stem and progenitor cells to restenosis, vascular repair, and atherosclerosis, on cell cycle regulation, on arterial remodeling, and on the effects of endothelial nitric oxide synthase that all play significant roles in the progression of the disease.
The focus shifts in Part III to diagnostics, reviewing the recent advances in invasive and noninvasive imaging of stenotic lesions, which has emerged in the recent years as a promising alternative to conventional imaging. This will be discussed by, the very people who have pioneered this particular field of vascular imaging. The last two parts of this book explores the exciting processes, we and others recently have obtained in the treatment of this vexing clinical problem.
Part IV will discuss the clinical experience with applying pharmacotherapy, brachytherapy, eluting stents, and biodegradable stents in the prevention of restenosis. It will be then followed by chapters in Part V that describe the more daring, but neverthe- less stimulating advancements in applying biotechnology in the treatment of restenosis. The chapters discuss the use of different types of vectors, transgene regulatory systems, and antisense oligonucleotides in vascular gene therapy. The use of molecular inhibitors that target restenosis by affecting the cell cycle will also be discussed. Finally, the
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current available methods that are suitable for local gene delivery are explored in the final chapter.
With these chapters elaboratly discussing the current understanding on the patho- physiology, molecular and genetic base, and methods of diagnosis of restenosis, and presenting the current state-of-the-art management, including pharmacotherapy and interventional percutaneous approaches using brachytherapy, gene therapy, and drug- eluting stent technology, we believe that this book provides the reader with a complete overview of the basic and applied knowledge of restenosis, leading to better insight and decision-making in clinical practice.
Finally, we would like to thank the contributors for their time and efforts. Without them, this high quality work could not have been produced.
Chapter 1 / Unraveling the Complex Process of Restenosis 5
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