Endothelium Nitric Oxide And Atherosclerosis

The opening chapter of this book, by scientist Dr. Robert Furchgott, details the discovery of endothelium’s role in the vasodilator effect of acetycholine in 1978. Its subsequent identification as nitric oxide has been critical to cardiovascular medicine in understanding the regulation of vascular homeostasis. This simple observation won Dr. Furchgott a Nobel Prize in 1998. Spanning from these initial observations to recent clinical investigations, this work offers an invaluable historical reference and clinical explanation about the intracellular mechanisms that regulate and stimulate endothelial nitric oxide synthase (eNOS). The basic mechanisms leading to endothelial dysfunction in cardiovascular disease complement information about the biological role and regulation of endothelial nitric oxide. Clinical studies of impaired endothelial function in patients with different cardiovascular conditions also reveal important and effective therapeutic strategies. Written for both established physicians and scientists investigating the basic mechanisms and treatment of cardiovascular disease, as well as medical students who want to initiate themselves in the study of endothelial regulation of vascular physiology, many will find this comprehensive review a stimulus for new research.

Comprehensive and in-depth in its coverage, Atherosclerosis: Cellular, Molecular & Biochemical Mechanism and Novel Therapy reviews the recent progress in atherosclerosis research and offers cutting edge perspectives from experts in the field. Written by an international team of authors including leading physician-scientists, research experts and physicians, chapters are divided into four major sections, covering risk factors, cellular and molecular mechanisms, biochemical mechanisms and novel and future therapeutics. Atherosclerosis: Cellular, Molecular & Biochemical Mechanism and Novel Therapy analyses recent progress from both conceptual and technological perspectives, suggesting new directions for atherosclerosis research and treatment for a growing population of researchers and clinicians in cardiovascular and related fields.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

A vast literature has been concerned with arteriosclerosis and yet, many aspects of pathogenesis and of the mechanism of development of the arteriosclerotic vascular lesion remain only poorly understood. In recent years, our knowledge of the earliest stages of arteriosclerosis have greatly improved. By now, we have learned to relate morphologic changes to disturbances in function. It has been of particular impor tance that components of the arterial wall could be analyzed in regard to dysfunction, for example, in the endothelium or the vascular smooth muscle. The interaction of the different morphological components of the vascular wall could thus be much bet ter understood. Likewise, the interaction between the arterial wall and the flowing blood could be much better described, including the intimate relationship between platelets and the endothelium, the coagulation system and the endothelium, the granulocytes and the endothelial cell layer, as well as processes of migration of blood cells into the subendothelial space. The recognition of functional and morphological disturbance has attained clinical significance not only because the arteriosclerotic diseases have quantitatively reached the dimensions of an epidemic, that is, of a magnitude never been witnessed. It is also because of the development of new drugs that interfere with the atherogenic process and thereby prevent the development of the disease or halt its progression. It is also becoming increasingly possible to inhibit the occurrence of complications in existing arteriosclerotic lesions in manifest disease, i. e.

Since the endothelium plays such an important role in the pathophysiology of the circulatory system, the readers attention is directed here towards the possible involvement of these polypeptides in the aetiology of ischaemic heart disease, cerebrovascular accidents, hypertension, atherosclerosis and renal failure.

The vascular endothelium has become an increasing focus of research over the last 15 years. Nitric oxide and endothelin appear to have important and opposing actions on vascular tone, smooth muscle proliferation and platelet/monocyte activation, and endothelial dysfunction affecting the L-arginine/nitric oxide and endothelin systems both appear to be crucial to atherogenesis and to the pathophysiology of many forms of cardiovascular disease. Additionally, a number of new drugs of major clinical interest are now emerging that act favourably to modulate endothelial function and alter the outcome in these conditions. Here, a synthesis of the current understanding of endothelial dysfunction in hypertension and related disorders - and future therapeutic prospects - has been drawn together by a series of internationally recognised leaders in the field.

Endothelial dysfunction is broadly defined as a disruption of the balance between vasoactive mediators and a propensity towards an inflammatory state. This volume provides an overview of the fields of endothelial dysfunction and inflammation through the discussion of topics ranging from the molecular biology of activated endothelial cells to the endothelium in inflammatory disease and therapeutic approaches targeting endothelial dysfunction. Topics include: Heterogeneity of the endothelium during inflammation, oxidative stress and endothelial dysfunction, biology and regulation of nitric oxide in inflammatory pathologies, endothelial dysfunction in inflammatory diseases, such as diabetes and atherosclerosis and Clinical methods used to assess endothelial function. This book brings together basic and clinical research to assist the reader in bridging connections from bench-to-bedside. Written by expert researchers in the fields of endothelial biology, inflammation research and clinical science, it serves as a useful reference for academic and industrial researchers, clinicians, and trainees in the medical profession.

Research on the key mediator nitric oxide has increased exponentially over the last ten years. It is now clear that, in addition to its role within the cardiovascular system, this mediator is also implicated in the normal physiological function and disease pathology of several organs and systems. A number of the fundamental research observations are now being developed into therapeutic principles and these are being pursued through clinical trials. This is the first work summarizing, in its two volumes, the quantum leap from basic science to clinical applications emerging from this decade of research.