The Endothelium Part I

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

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

The endothelium controls vascular tone by releasing various vasoactive substances. Additionally, another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells contributes also to endothelium-dependent relaxations (EDHF-mediated responses). These responses involve an increase in the intracellular Ca concentration of the endothelial cells followed by the opening of Ca-activated K channels of small and intermediate conductances (SKCa and IKCa). These channels show a distinct subcellular distribution, suggesting that their activation could be elicited by distinct stimuli. Following KCa activation, the endothelial hyperpolarization can be conducted to the underlying smooth muscle cells by electrical coupling through myo-endothelial gap junctions. In addition, the potassium efflux can lead to the accumulation of potassium ions in the intercellular space and the subsequent activation of smooth muscle Kir2.1 and/or Na/K-ATPase. The hyperpolarization of the smooth muscle cells produces vascular relaxation, predominantly by closing voltage-gated calcium channels, and vasodilatation. EDHFmediated responses are altered in various pathologies or, conversely, act as a compensating mechanism when other endothelial pathways are impaired. A better characterization of EDHF-mediated responses should allow determining whether or not new drugable targets can be identified within this endothelial pathway for the treatment of cardiovascular diseases. Table of Contents: Endothelium-Dependent Hyperpolarizations: The Classical "EDHF" Pathway / Conclusion / References

The endothelium controls vascular tone by releasing various vasoactive substances. Additionally, another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells contributes also to endothelium-dependent relaxations (EDHF-mediated responses). These responses involve an increase in the intracellular Ca concentration of the endothelial cells followed by the opening of Ca-activated K channels of small and intermediate conductances (SKCa and IKCa). These channels show a distinct subcellular distribution, suggesting that their activation could be elicited by distinct stimuli. Following KCa activation, the endothelial hyperpolarization can be conducted to the underlying smooth muscle cells by electrical coupling through myo-endothelial gap junctions. In addition, the potassium efflux can lead to the accumulation of potassium ions in the intercellular space and the subsequent activation of smooth muscle Kir2.1 and/or Na/K-ATPase. The hyperpolarization of the smooth muscle cells produces vascular relaxation, predominantly by closing voltage-gated calcium channels, and vasodilatation. EDHFmediated responses are altered in various pathologies or, conversely, act as a compensating mechanism when other endothelial pathways are impaired. A better characterization of EDHF-mediated responses should allow determining whether or not new drugable targets can be identified within this endothelial pathway for the treatment of cardiovascular diseases. Table of Contents: Endothelium-Dependent Hyperpolarizations: The Classical "EDHF" Pathway / Conclusion / References

The endothelium, the cell layer that forms the inner lining of blood vessels, is a spatially distributed system that extends to all areas of the human body. Clinical and basic research demonstrates that the endothelium plays a crucial role in mediating homeostasis and is involved in virtually every disease, either as a primary determinant of pathophysiology or as a victim of collateral damage. The endothelium has remarkable, though largely untapped, diagnostic and therapeutic potential. This volume bridges the bench-to-bedside gap in endothelial biomedicine, advancing research and development and improving human health. The book is the first to systematically integrate knowledge about the endothelium from different organ-specific disciplines, including neurology, pulmonary, cardiology, gastroenterology, rheumatology, infectious disease, hematology-oncology, nephrology, and dermatology. It's interdisciplinary approach, which draws on expertise from such diverse fields as evolutionary biology, comparative biology, molecular and cell biology, mathematical modeling and complexity theory, translational research, and clinical medicine.

Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes provides an in-depth examination of the role of endothelium and endothelial dysfunction in normal vascular function, and in a broad spectrum of clinical syndromes, from atherosclerosis, to cognitive disturbances and eclampsia. The endothelium is a major participant in the pathophysiology of diseases, such as atherosclerosis, diabetes and hypertension, and these entities are responsible for the largest part of cardiovascular mortality and morbidly. Over the last decade major new discoveries and concepts involving the endothelium have come to light. This important reference collects this data in an easy to reference resource. Written by known experts, and covering all aspects of endothelial function in health and disease, this reference represents an assembly of recent knowledge that is essential to both basic investigators and clinicians. Provides a complete overview of endothelial function in health and diseases, along with an assessment of new information Includes coverage of groundbreaking areas, including the artificial LDL particle, the development of a new anti-erectile dysfunction agent, a vaccine for atherosclerosis, coronary calcification associated with red wine, and the interplay of endoplasmic reticulum/oxidative stress Explores the genetic features of endothelium and the interaction between basic knowledge and clinical syndromes

There can no longer be any doubt that the endothelium represents a very active tissue and is not, as had previously been thought, merely an inert lining material. On the contrary, the endothelium exerts a powerful influence on its environs through the release of multiple regulatory factors such as nitric oxide, endothelium derived hyperpolarizing factor and endothelin. It is therefore crucial to our understanding of the cardiovascular system that we are able to visualize the endothelial layer at the molecular level. Quantitative morphological studies permit visualization at this level, allowing the assessment of the changes that occur in the disease state. Modern methods of computerized image analysis have been applied to reconstruct the endothelial layer in three-dimensions - detecting even the most subtle of changes. Within these covers, an integrated text has been gathered by experts in each of their fields. They detail the latest technical and conceptual advances in the visualization of endothelium, its production of regulatory molecules and pathological changes.