Pathogenesis Of Atherosclerosis

This book provides new perspectives on the pathogenesis of atherosclerosis. Chapters cover atherosclerosis risk factors, the effect of growth and aging on vascular architecture, and the crucial role the microvasculature plays in atherosclerosis development. Microvascular dysfunction would explain why the well-known risk factors actually put individuals at higher risk. This pathomechanism would also hold true not only for obstructive atheroma formation but also for aneurysmal dilatation as well as for aortic and peripheral artery dissection. When seen through this lens, novel preventive and therapeutic opportunities can be envisioned. Atherosclerosis Pathogenesis and Microvascular Dysfunction proposes a single unifying mechanism of atherosclerosis development and describes potential preventative and therapeutic avenues based on this concept. It therefore represents a timely and valuable resource for internal medicine, cardiology, angiology cardiovascular surgeons, pathology clinicians, researchers, trainees, and students.

The circulatory system provides the tissues of the body with oxygen and nutrients for survival, allows for the dissemination of inflammatory cells, and clears metabolic waste from building up and damaging tissue. Atherosclerotic disease, the build-up of fat, inflammatory cells, and fibrotic tissue in the vessel wall, hinders this function, resulting in inadequate perfusion of the target tissue. Hypoxia, or lack of oxygen, rapidly results in cellular dysfunction that profoundly affects the functionality of the overall tissue. Atherosclerosis-associated tissue ischemia and hypoxia because of loss of blood flow underlies several significant disease pathologies including ischemic heart disease, stroke, and peripheral artery disease. In this eBook, we examine the process of atherosclerotic plaque formation both at the cellular level and the level of clinical presentation. Through this book, we hope to impart to the reader a better understanding of how vessel structure, environmental risk factors, and genetic predisposition contribute to atherosclerotic disease and how current and future therapies seek to circumvent the cellular processes contributing to plaque formation to reduce atherosclerotic plaque burden and clinical complications. Table of Contents: List of Videos / Introduction to Atherosclerosis / Epidemiology / Endothelial Cell Activation and Arterial Hemodynamics / Cholesterol and Cardiovascular Disease / Inflammation in Atherosclerosis / Smooth Muscle Cells and Plaque Vulnerability / Diagnosing Atherosclerotic Disease / Treatment and Prevention / Summary and Future Perspectives / References / Author Biographies

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.

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. Anincreasing 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 ischaemicstroke, 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 isreviewed 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 apractical approach to investigating patients with stroke for underlying genetic disorders. Also included is a list of useful websites.

Atherosclerosis is a chronic inflammatory disease that affects medium and large-sized arteries. It begins after birth and the progression depends on several factors - traditional triad: hypertension, hyperlipidemia and diabetes mellitus, then age, sex, smoking and sedentary life-style. At the beginning atherosclerosis is asymptomatic and we cannot estimate appropriately its frequency, but its complications - coronary artery diseases, cerebrovascular diseases, peripheral arterial diseases, which occur late, are responsible for more than half of the yearly mortality in the world. Unfortunately, sudden cardiac death may be the first clinical manifestation. The incipient event is endothelial dysfunction, as a result of injury, caused by high level of cholesterol [especially w-density-lipoprotein LDL], hyperglycemia, hypertension, smoking, infectious agents, and toxins. Endothelial cells overexpress adhesion molecules - vascular cell adhesion molecule-1 [VCAM-1] and increases recruitment of inflammatory cells - monocytes [Mo], T-cells and subsequent release of monocyte chemo-attractant protein-1 [MCP-1] that results in additional leucocytes recruitment. Injured endothelium allows migration of inflammatory cells that release cytokines and lipids into the intima. That leads to cytokine-mediated progression of atherosclerosis and oxidation of LDL. Macrophages [MP] take up oxi-LDL and form foam-cell. They have metabolic activity and produce cytokines, proliferation of smooth muscle cells and formulate athero-fibrose plaque. Atherosclerotic plaque is composed of superficial layer - fibrose cap and lipid core, that consists of foam cells, extracellular lipid and necrotic cellular debris. It progresses as a result of accumulation of lipid and proliferation of smooth muscle cells and results in luminal narrowing of the arteries which leads to compromised blood and oxygen supply to the tissues. The gradually growing atherosclerotic plaques have thick fibrose cap and are stable. They cause symptoms of stable angina. Rapidly growing plaques cause unstable coronary artery disease. These plaques are mainly composed of lipids and have tiny fibrose cap that is prone to fissuring or rupture. Intraplaque hemorrhage from microvessels in plaque initiate platelet adhesion and activation of coagulation cascade that leads to platelet thrombus formation, i.e. promote thrombogenesis. Knowledge of the pathogenesis of the atherothrombosis modifies the diagnostic and therapeutic approach. Conclusion: Attention should be focused on the management of three points: 1. Endothelial dysfunction [correction of modified risk factors: hypertension, hyperlipidemia, diabetes mellitus, life-style-smoking, physical activity and food], 2. Atherosclerosis [modification of the inflammatory cascade, i.e. elimination of inflammatory pathways and inhibition of oxidation of LDL], 3. Thrombogenesis [inhibition of platelet adhesion, activation and aggregation].

Cardiovascular diseases continue to be the leading cause of death in the - jority of industrialized countries. The most frequent underlying pathology, namely atherosclerosis, and its clinical sequelae, namely coronary heart d- ease, cerebrovascular disease and peripheral artery disease, remain common although for a long time we have been made aware of avoidable or mo- ?able etiological factors such as smoking, fat-rich diet or lack of exercise, and although these adverse lifestyle factors have been extensively addressed by population-wide primary prevention programs. Cardiovascular morbidity and mortality also remain high despite successful anti-hypertensive and lipid lowering drug therapies which help to reduce cardiovascular morbidity and mortality by about 30% in both secondary and tertiary prevention settings. This can partly be explained by the increasing life expectancy and growing p- portionofelderly people,especiallyinEuropeandNorthAmerica. Inaddition, the World Health Organization makes the alarming prediction that probably in response to the spreading of western dietary behavior and lack of exercise resulting in an increasing prevalence of diabetes, dyslipidemia and hypert- sion, cardiovascular diseases rather than infectious diseases will become the most frequent cause of death worldwide. This volume of the Handbook of Experimental Pharmacology entitled “Atherosclerosis” is divided into four parts and intends to give an overview on the pathogenesis of atherosclerosis, established treatment and prevention regimen, and of perspectives for the development of new treatment modalities.

Intracranial atherosclerosis is a leading cause of stroke in Asians and Africans. As these ethnic groups account for more than 70% of the world’s population, it is in fact the major cause of ischemic stroke worldwide. This timely book provides readers with up-to-date knowledge of intracranial atherosclerosis, covering vascular anatomy, pathology, epidemiology, stroke mechanisms and syndromes, diagnostic methods as well as treatment strategies such as antithrombotics, angioplasty/stenting and surgery. Furthermore, nonatherosclerotic intracranial arterial diseases like Moyamoya disease, dissection, vasculitis and other miscellaneous disorders are extensively discussed. Experts from both East and West present the latest findings from cutting-edge research and discuss controversial topics from different yet balanced points of view, allowing readers to form their own unbiased opinion on these issues. With this approach, the book serves as a useful and stimulating guide on the diagnosis and management of intracranial atherosclerosis for neurologists, neurosurgeons, neuroradiologists and vascular interventionists.