It has been known for over 150 years that hallmarks of inflammation can be observed in the wall of atherosclerotic vessels. It was, however, not clear if this inflammation is the cause or the consequence of atherogenesis. More recently, it has become evident that inflammation mediated both by innate and adaptive immunity is instrumental even in the earliest stages of the development of atherosclerotic lesions, i.e., that it plays an important pathogenetic role. In this volume, international experts in the field discuss the pathogenetic, diagnostic, preventive and possible therapeutic relevance of inflammation in atherogenesis. This book is intended for researchers and physicians in the fields of vascular biology, immunology and atherosclerosis.

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.

This textbook focuses on the vascular biology and physiology that underlie vascular disorders in clinical medicine. Vascular biomedicine is a rapidly growing field as new molecular mechanisms of vascular health and disease are unraveled. Many of the major cardiovascular diseases including coronary artery disease, heart failure, stroke and vascular dementia are diseases of the vasculature. In addition vascular injury underpins conditions like kidney failure and cardiovascular complications of diabetes. This field is truly multidisciplinary involving scientists in many domains such as molecular and vascular biology, cardiovascular physiology and pharmacology and immunology and inflammation. Clinically, specialists across multiple disciplines are involved in the management of patients with vascular disorders, including cardiologists, nephrologists, endocrinologists, neurologists and vascular surgeons. This book covers a wide range of topics and provides an overview of the discipline of vascular biomedicine without aiming at in-depth reviews, but rather offering up-to-date knowledge organized in concise and structured chapters, with key points and pertinent references. The structure of the content provides an integrative and translational approach from basic science (e.g. stem cells) to clinical medicine (e.g. cardiovascular disease). The content of this book is targeted to those who are new in the field of vascular biology and vascular medicine and is ideal for medical students, graduate and postgraduate students, clinical fellows and academic clinicians with an interest in the vascular biology and physiology of cardiovascular disease and related pathologies.

In this eBook, we have grouped together 16 original contributions which have addressed the translational potential for therapeutics developed on the conceptual framework of the resolution of inflammation. The take home message of our effort, and the efforts of our colleagues who wrote these pieces, is that completely different drugs can be designed and modelled on the mediators and targets of resolution. By implementing this 180° shift in the way we plan the drug development programme (that is by focusing on agonists and/or promoting the actions of pro-resolution agonists) we can offer a fresh approach to the clinical management of chronic diseases that affect the modern society. With this series of articles we foresee the birth of Resolution Pharmacology. The 16 contributions presented herein confirm the broad relevance of pro-resolving physio-pharmacology with the description of pro-resolving mechanisms in distinct diseases, from atherosclerosis and heart infarct, to cystic fibrosis and diabetes. This testifies on one hand the fundamental role that inflammatory mechanisms play in virtually all pathological settings and, on the other hand, the great potential that a novel approach to anti-inflammatory therapy by exploiting resolution mediators and targets may have. Thus, while there is broad recognition that evidence-based interventions have transformed cardiovascular, inflammation and endocrine care, new therapies are still needed for growing numbers of patients with unmet needs. As an example, an estimated 17 million people world-wide die annually of cardiovascular diseases, particularly heart attacks and strokes. Cardiovascular diseases occur almost equally in men and women and are the leading cause of death and morbidity worldwide. It is estimated that only 1/1,000 compounds entering preclinical testing are then trialled in man and the actual cost of developing a new therapeutic into clinical practice has grown exponentially over the past two decades (estimated $1.2B). Over the last 20 years or more, scientists have appreciated the biology of the resolution of inflammation, which provides a new paradigm in our understanding of the inflammatory process with the appreciation of genetic, molecular and cellular mechanisms that are engaged to actively resolve inflammation. The ‘resolution of acute inflammation’ is enabled by counter-regulatory checkpoints to terminate the host reaction while at the same time promoting healing and repair. The potential of lipid mediators to enact pro-resolving effects in the context of cystic fibrosis is presented by Recchiuti et al., while Fredman reasons on the potential for these molecules in atherosclerosis. This resonates well with the contributions from Bäck and colleagues who have focused on pro-resolving receptors to offer vasculo-protection in intimal hyperplasia and more generally in cardiovascular disease. On the same vein is the scholar contribution of Leoni and Soehnlein who focus on heart disease, with Qin et al. presenting the latest findings on the effect of an Annexin A1-derived peptide in myocardial infarction. Hansen et al. and de Gaetano et al. bring in the complexity of diabetes and associated morbidity with a focus on specialised pro-resolving lipid mediators but also introducing the potential of dietary approaches. As the western diet favours disease, an omega-3 rich diet can lead to higher availability of lipid mediators to afford tissue protection if not reverting its pathological status. Docosahexaenoic acid and its bioactive derivatives are endowed with potent anti-nociceptive properties following bone fracture, as shown by Zhang et al. The broad relevance of the pharmacological approach reaches the skin with Resolvin D1 protecting against UV irradiation (Saito et al.). Reduced skin inflammation is also achieved with an Annexin A1 peptide that impacts on the outcome of heterologous transplantation (Lacerda et al.). Indeed, modulating the phenotype of immune cells can provide long lasting beneficial outcomes, as attained with CDK inhibitors (Cartwright et al.) and PI3K inhibitors in experimental gout (Galvao et al.). Such an effect is also achieved with a third group of pro-resolving therapeutics, the melanocortin receptor agonists, with important modulation of macrophage reactivity (Patruno et al.) with Spana et al., providing new pharmacology following selective activation of the MC1 receptor. Finally, Hopkin et al. discuss the potential for targeting immune cell trafficking as a way to control immune mediated diseases, bringing in not only pro-resolving mediator agonists, but also approaches to reduce chemo/cytokine gradients or modulating S1P and 11-beta hydroxysteroid dehydrogenase. Finally, we wish to highlight that this wealth of science has also bought to the forefront specific pro-resolving receptors (including FPR2/ALX, GPR32, ChemR23 and MC1), all G protein coupled receptors that are therefore amenable to pharmacological exploitation for drug discovery programmes. We see that not only agonists to the receptors can be developed, some of them modelled on the natural ligands (e.g. resolvins, lipoxins, Annexin A1-derived peptides or melanocortin peptides), but also that the creativity of this pharmacology can be attained through biased ligands and positive allosteric modulators. Deep knowledge of pro-resolving receptor biology and their cell-specific signalling can accelerate the generation of novel anti-inflammatory depicted on the resolution of inflammation. In conclusion, with this eBook, we propose time is ready to exploit the concepts of resolution and use its targets and mediators for the identification of better drugs to establish ‘Resolution Pharmacology’. We predict Resolution Pharmacology will represent an important innovation in the way common diseases will be treated in the next decades of this millennium.

Endorsed by the American Society for Preventive Cardiology, this highly practical resource focuses on the application of current guidelines and practice standards in the clinical management of cardiovascular risk factors. The Manual presents concise descriptions of each major cardiovascular risk factor, and practical, to-the-point discussions of current best practices in clinical management. In addition, the Manual includes chapters on peripheral arterial disease, stroke, smoking, contemporary cardiovascular imaging, heart failure, metabolic syndrome, thrombosis, nutrition, special populations, novel risk factors, and psychosocial stress. Throughout the Manual, recommendations are based on the most recent prevention guidelines of the American College of Cardiology and American Heart Association, including those on Risk Assessment, Lifestyle Recommendations, Blood Cholesterol, and Obesity, as well as the new guidelines on Hypertension. Chapter authors are recognized leaders in each area of practice, and special efforts have been made by the authors and editors to ensure that the content of all chapters is as up-to-date as possible. Key Features: Presents a highly practical focus on the application of current guidelines and practice standards regarding cardiovascular risk factors Recommendations based on the most recent prevention guidelines Authored by recognized leaders in the field Covers all major cardiovascular risk factors, key methodologies in risk assessment, and special issues regarding specific patient populations

Inflammation in Heart Failure, edited by W. Matthijs Blankesteijn and Raffaele Altara, is the first book in a decade to provide an in-depth assessment on the causes, symptoms, progression and treatments of cardiac inflammation and related conditions. This reference uses two decades of research to introduce new methods for identifying inflammatory benchmarks from early onset to chronic heart failure and specifically emphasizes the importance of classifying at-risk subgroups within large populations while determining the patterns of cytokines in such classifications. Further, the book details clinical applications of the pathophysiological mechanisms of heart failure, diagnosis and therapeutic strategies. Inflammation in Heart Failure's breadth of subject matter, easy-to-follow structure, portability, and high-quality illustrations create an accessible benefit for researchers, clinicians and students. - Presents updated information and research on the relevant inflammatory mediators of heart failure to aid in targeting future translational research as well as the improvement of early diagnosis and treatment - Provides research into better understanding the different inflammatory mediators that signal the underlying diseases that potentially lead to heart failure - Contains 20 years of research, offering a brief overview of the topic leading to current opinions on, and treatment of, heart failure - Provides a structured, systematic and balanced overview of the role of inflammation in heart failure making it a useful resource for researchers and clinicians, as well as those studying cardiovascular diseases

Presenting further studies in the prevention and treatment of coronary artery disease, this book brings together the knowledge accrued in the past decade concerning the role of immunity in the initiation and perpetuation of atherosclerosis. A strong group of international contributors summarize the diverse aspects of the interrelationship between the immune system and atherosclerosis.

Stroke is a major cause of death and the major cause of adult neurological disability in most of the world. Despite its importance on a population basis, research into the genetics of stroke has lagged behind that of many other disorders. However, the situation is now changing. An increasing number of single gene disorders causing stroke are being described, and there is growing evidence that polygenic factors are important in the risk of apparently "sporadic" stroke. Stroke Genetics provides an up-to-date review of the area, suitable for clinicians treating stroke patients, and both clinical and non-clinical researchers in the field of cerebrovascular disease. The full range of monogenic stroke disorders causing cerebrovascular disease, including ischaemic stroke, intracerebral haemorrhage, aneurysms and arteriovenous malformations, are covered. For each, clinical features, diagnosis, and genetics are described. Increasing evidence suggest that genetic factors are also important for the much more common multifactorial stroke; this evidence is reviewed along with the results of genetic studies in this area. Optimal and novel strategies for investigating multifactorial stroke, including the use of intermediate phenotypes such as intima-media thickness and MRI detected small vessel disease are reviewed. The book concludes by describing a practical approach to investigating patients with stroke for underlying genetic disorders. Also included is a list of useful websites.