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Endothelial Signaling in Vascular Dysfunction and Disease

Endothelial Signaling in Vascular Dysfunction and Disease
From Bench to Bedside

by Shampa Chatterjee

  • Publisher : Academic Press
  • Release : 2021-01-20
  • Pages : 274
  • ISBN : 0128163828
  • Language : En, Es, Fr & De
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Endothelial Signaling in Vascular Dysfunction and Disease: From Bench to Bedside provides a detailed understanding of the endothelium, its activation and their link to some common clinical disorders. In addition, the book covers earlier discoveries, including those from the last and 19th centuries. It is split into five sections that cover the vascular tree as an integrative structure, the endothelium in inflammation, endothelial signaling, activation and toxicity with chemotherapy, radiation induced endothelial dysfunction and vascular disease, and therapies in combating vascular diseases. Each section is discussed with a translational approach in order to make the content truly applicable. This book is a valuable source for basic researchers, clinicians in the fields of Oncology, Cardiovascular Medicine and Radiology, and members of the biomedical field who are conducting studies related to the endothelium and vascular disease. Discusses the most relevant discoveries in endothelial biology and their link to manifestations of clinical disease Presents history and diagrams in each section to highlight the original biological discovery and its link of clinical manifestations of vascular disease Includes recent findings on the relationship between endothelial signaling, chemotherapy and radiation induced endothelial dysfunction

Endothelial Cells in Health and Disease

Endothelial Cells in Health and Disease
A Book

by William C. Aird

  • Publisher : CRC Press
  • Release : 2005-02-28
  • Pages : 512
  • ISBN : 1135534608
  • Language : En, Es, Fr & De
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This reference serves as the first source to gather current data from endothelial cell biologists in various disciplines to summarize recent progress in the field-providing a complete understanding of the endothelium in health and disease and demonstrating its potential as a therapeutic target.

Vascular Dysfunction Beyond Pathological Pregnancies. An International Effort Addressed to Fill the Gaps in Latin America

Vascular Dysfunction Beyond Pathological Pregnancies. An International Effort Addressed to Fill the Gaps in Latin America
A Book

by Carlos Alonso Escudero,Fernanda Regina Giachini,Carlos Galaviz-Hernandez,Alicia E. Damiano

  • Publisher : Frontiers Media SA
  • Release : 2019-11-22
  • Pages : 136
  • ISBN : 2889632016
  • Language : En, Es, Fr & De
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Pregnancy is a physiologically stressful condition that generates a series of functional adaptations in the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia; gestational diabetes; growth restriction; autoimmune diseases; among others, affect the function of the maternal and offspring vascular systems, after delivery and may be extended until adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. In Latin American countries, like other low (LIC) and middle-income countries (MIC) worldwide, the rate of morbi-mortality due to both pregnancy complications and cardiovascular diseases have a higher incidence than in high-income countries (HIC). But, investigation in LIC and MIC, in particular in Latin America, still fall short of what would be expected considering the magnitude of those diseases. Although there are obvious deficiencies in terms of economies and scientific infrastructure between HIC and MIC or LIC, Latin American strength in terms of scientific productivity in this filed could be underestimated due to language limitation and publication in journals not indexed in major citation databases, resulting in low impact publications. As a result, we could speculate that potentially unique features of vascular disease associated to pregnancies complications can be unnoted in the global scientific community. Then, we would like to encourage researchers in vascular biology, in which, many groups in Latin America have contributed to both better understand vascular dysfunction associated to pregnancy diseases and show the gaps in the literature, to overcome this hidden effect of our scientific production. This effort also will homogenize clinical concepts and knowledge that may strength the scientific effort in Latin America.

Mechanisms of Vascular Defects in Diabetes Mellitus

Mechanisms of Vascular Defects in Diabetes Mellitus
A Book

by C.C. Kartha,Surya Ramachandran,Radhakrishna M. Pillai

  • Publisher : Springer
  • Release : 2017-08-01
  • Pages : 579
  • ISBN : 3319603248
  • Language : En, Es, Fr & De
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This book intends to bring together, a panel of renowned experts in the field of vascular biology and diabetology, to integrate the current understanding of the pathogenesis and pathophysiology of vascular diseases in diabetes mellitus. This attempt is significant given the increasing interest in this area as the prevalence of vascular diseases continues to escalate globally. Patients with diabetes are at a higher risk of structural and functional changes in all vessel walls of the human body. Vascular complications of diabetes are leading causes for both morbidity and mortality. In recent years, several articles have focused on advancing our knowledge on the profound effect of hyperglycemia and insulin resistance on building up vascular wall inflammation leading to endothelial dysfunction in patients with diabetes mellitus Other reports have elaborated on the various disorders, hyperglycemia can lead to, their therapies, adverse effects and complications. There are also studies that highlight the role of factors that induce vascular wall alterations in hyperglycemia. In this book, we attempt to discuss vascular disease progression in diabetes with a unique approach. We attempt to provide a complete perspective of the pathophysiology of vascular complications and then dissect each of the factors that play a key role in accelerating vascular wall alterations in diabetes. Each of these factors has been adversely implicated in the initiation and progression of disease to a large extent. In this collection for the first time all these factors would be described under a common canopy. Further, the text would emphasize on pathogenesis of micro vascular complications of diabetes, such as retinopathy, neuropathy and nephropathy. Pharmacological therapies for treating vascular dysfunction in diabetes mellitus would also be reviewed. This compendium hopefully would be an invaluable replacement to scores of literature on diabetic vascular disease and would be of great interest to clinicians, academicians, medical students and researchers. The book will be divided into seven sections, each emphasizing a common incentive to development of vascular disease in diabetes. Section I deals with pathophysiology of diabetic vascular disease, beginning with an update on the global burden of diabetes mellitus and its vascular complications. The pathophysiology and pathogenesis of diabetes associated macrovasculopathy, how hyperglycemia functions as an atherogenic factor, effects of hyperglycemia on smooth muscle accumulation in vascular lesions and genetic susceptibility for increased risk of vascular disease in diabetes will be discussed in the following chapters of this section. The next section (Section II) surveys the process of endothelial dysfunction under hyperglycaemia and hyperinsulinemia and their effects on angiogenesis, vascular remodeling and wound healing. A chapter is also dedicated to the endothelial progenitor cell population and its dysfunction during development of vascular complications in diabetes. Section III will highlight the molecular mechanisms underlying endothelial dysfunction, various pathways such as nitric oxide synthase pathway, oxidative stress pathway, renin – angiotensin system and increased vascular superoxide production in the initiation and progression of vascular disease in diabetes. This section also covers role of endothelin, monocyte derived cytokines, peroxynitrate and adipokines in macrovascular complications of diabetes. Metabolic factors such as advanced glycation end products, atherogenic dyslipoproteinaemia, and homocysteine will be reviewed in Section IV, whereas an overview of the hemostatic factors such as platelet dysfunction, hyperglycaemia induced thrombin formation and aberrant clot lysis will be dwelled upon in Section V.Section VI includes chapters on microvascular complications of diabetes which encompasses long term complications of diabetes affecting small blood vessels of the eye, kidneys and nervous system. The pathogenesis and mechanisms of these complications would be detailed here. The final section (Section VII) of the book will consider mechanism of action of drugs for treating endothelial dysfunction in diabetes mellitus which would elaborate on lipid regulating therapies such as statins, as well as other therapies such as ACE inhibitors, Angiotensin II receptors, insulin, metformin and their effects on enhancing vascular function in diabetes.“/div>divWe intend to invite authors who symbolize a multidisciplinary approach to this complicated disease. The proposed authors include clinicians who understand the trend of vascular complications in their long term clientele, epidemiologists with a holistic view, basic and experimental researchers with years of experience in dissecting the factors leading to endothelial dysfunction and clinical researchers with the skill of translating bench work to the bedside. We expect this book will be of significant value and interest to the same group of clinicians, researchers, post doctoral fellows and medical and non medical graduate students. The novel assimilated insights could stimulate development of mechanism based prevention and therapeutic strategies providing a promising option to limit cardiovascular complications in diabetes mellitus.

Mechanisms of Over-active Endothelium-derived Contracting Factor Signaling Causing Common Carotid Artery Endothelial Vasomotor Dysfunction in Hypertension and Aging

Mechanisms of Over-active Endothelium-derived Contracting Factor Signaling Causing Common Carotid Artery Endothelial Vasomotor Dysfunction in Hypertension and Aging
A Book

by Steven Garfield Denniss

  • Publisher : Unknown Publisher
  • Release : 2011
  • Pages : 216
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Background and Purpose: The endothelium is a single-cell layer positioned at the blood-vascular wall interface, where in response to blood-borne signals and hemodynamic forces, endothelial cells act as central regulators of vascular homeostatic processes including vascular tone, growth and remodeling, inflammation and adhesion, and blood fluidity and coagulation. Agonist- or flow-stimulated endothelium-dependent vasorelaxation becomes impaired in states of cardiovascular disease (CVD) risk and has been identified as a possible biomarker of overall endothelial dysfunction leading to vascular dysregulation and disease pathogenesis. Accordingly, it is important to elucidate the mechanisms accounting for this endothelial vasomotor dysfunction. Upon stimulation, endothelial cells can synthesize and release a variety of endothelium-derived relaxing factors (EDRFs), the most prominent of which is nitric oxide (NO) derived from NO synthase (NOS). In addition, under certain CVD risk conditions including hypertension and aging, stimulated endothelial cells can become a prominent source of endothelium-derived contracting factors (EDCFs) produced in a cyclooxygenase (COX)-dependent manner. Consequently, endothelial dysfunction may be caused by under-active EDRF signaling and/or competitive over-active EDCF signaling. Much attention has been given to elucidating the mechanisms of under-active EDRF signaling and its role in causing endothelial dysfunction, wherein excess reactive oxygen species (ROS) accumulation and oxidative stress under CVD risk conditions have been recognized as major factors in reducing NO bioavailability thus causing under-active EDRF signaling and endothelial dysfunction. Less attention however, has been given to elucidating the mechanisms of over-active COX-mediated EDCF signaling and its role in causing endothelial dysfunction. Moreover, while COX-mediated EDCF signaling activity has been investigated in some segments of the vasculature, most notably the aorta, it has not been well-investigated in the common carotid artery (CCA), a highly accessible cerebral blood flow conduit particularly advantageous in exploring the roles of the endothelium in vascular pathogenesis. It was the global purpose of this thesis to gain a better understanding of the cellular-molecular mechanisms accounting for endothelial dysfunction in the CCA of animal models known to exhibit COX-mediated EDCF signaling activity, in particular essential (spontaneous) hypertension and aging. Experimental Objective and Approach: This thesis comprises three studies. Study I and Study II investigated the CCA of young-adult (16-24wk old) normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats. Study III investigated the CCA of Adult (25-36wks old) and Aging (60-75wks old) Sprague Dawley (SD) rats treated in vivo (or not; CON) with L-buthionine sulfoximine (BSO) to chronically deplete the cellular anti-oxidant glutathione (GSH) and increase ROS accumulation and oxidative stress. The global objective and approach across these studies was to systematically examine the relative contributions of NOS and COX signaling pathways in mediating the acetylcholine (ACh)-stimulated endothelium-dependent relaxation (EDRF) and contractile (EDCF) activities of isometrically-mounted CCA in tissue baths in vitro, with a particular focus on elucidating the mechanisms of COX-mediated EDCF signaling activity. An added objective was to examine the in vivo hemodynamic characteristics of the CCA in each animal model investigated, serving both to identify the pressure-flow environment that the CCA is exposed to in vivo and to provide assessment of potential hypertension, aging, and oxidative stress effects on large artery hemodynamics. Key Findings: Study I hemodynamic analysis confirmed a hypertensive state in young adult SHR while also exposing a reduction in mean CCA blood flow in SHR compared to WKY accompanied by a multi-faceted pressure-flow interaction across the cardiac cycle relating to flow and pressure augmentation. Study III hemodynamic analysis found that neither aging nor chronic BSO-induced GSH depletion affected CCA blood pressure or blood flow parameters in SD rats. Study I and II demonstrated that a COX-mediated EDCF response impaired ACh-stimulated endothelium-dependent vasorelaxation in pre-contracted CCA from young adult SHR, while EDRF signaling activity, predominantly mediated by NO, remained well-preserved compared to WKY. Examining ACh-stimulated contractile function specifically from a quiescent (non pre-contracted) state revealed that EDCF activity did exist in WKY CCA but could be completely suppressed by NO-mediated EDRF signaling activity, whereas the similarly robust NO-meditated EDRF signaling activity in SHR CCA could not fully suppress its >2-fold augmented EDCF activity vs. WKY CCA. Further pharmaco-dissection of ACh-stimulated contractile function in the SHR-WKY CCA model revealed that the EDCF signaling activity was completely dependent on the COX-1 (but not COX-2) isoform of COX and was almost exclusively mediated by the thromboxane-prostanoid (TP) sub-type of the prostaglandin (PG) G-protein coupled receptor family and by Rho-associated kinase (ROCK), a down-stream effector of the molecular switch RhoA. Furthermore, it was found that while exogenous ROS-stimulated CCA contractile function was similarly >2-fold augmented in SHR vs. WKY and dependent on COX-1 and TP receptor and ROCK effectors, ACh-stimulated CCA EDCF signaling activity was only minimally affected by in-bath ROS manipulating compounds. Additional biochemical and molecular analysis revealed that ACh stimulation was associated with PG over-production from an over-expressed COX-1 in SHR CCA, and with CCA plasma membrane localization and activation of RhoA. Study III demonstrated that a COX-mediated EDCF response impaired ACh-stimulated endothelium-dependent vasorelaxation in pre-contracted CCA from Aging SD rats, while EDRF signaling activity, predominantly mediated by NO, remained well-preserved compared to Adult SD rats. Specific examination of ACh-stimulated contractile function revealed that EDCF activity did exist in Adult CCA but could be completely suppressed by NO-mediated EDRF signaling activity, whereas the similarly robust NO-meditated EDRF signaling activity in Aging CCA could not fully suppress its >3-fold augmented EDCF activity vs. Adult CCA. Further pharmaco-dissection of ACh-stimulated contractile function in the Adult-Aging SD rat CCA model revealed that EDCF signaling activity was completely dependent on COX-1, but while exogenous ROS was able to elicit a COX-dependent CCA contractile response, in-bath ROS manipulating compounds were found to be without effect on ACh-stimulated CCA EDCF signaling activity. Furthermore, biochemical analysis revealed that aging was not associated with a change in tissue (liver and vascular) GSH content or ROS accumulation. Chronic in vivo BSO treatment was effective in depleting tissue GSH content and increasing ROS accumulation, to a similar extent, in both Adult and Aging SD rats. However, regardless of age, neither ACh-stimulated NO-mediated EDRF signaling activity nor COX-mediated

Peripheral Arterial Disease

Peripheral Arterial Disease
Pathophysiology and Therapeutics

by Christopher G. Kevil,Shyamal C. Bir,Christopher B. Pattillo

  • Publisher : Biota Publishing
  • Release : 2013-08-01
  • Pages : 82
  • ISBN : 1615045996
  • Language : En, Es, Fr & De
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Peripheral arterial disease (PAD) is a cardiovascular disorder of the peripheral vasculature due to progressive atherosclerotic stenosis of conduit arteries restricting blood flow to tissues. PAD is typically a disease of older individuals, and the incidence of PAD continues to rise due to an increase in cardiometabolic disease and an aging population. Importantly, “all cause” and cardiovascular morbidity and mortality are significantly increased in PAD patients. PAD diagnosis remains a significant challenge, as a large number of patients are asymptomatic. Moreover, PAD results in a significant financial and societal burden with underutilized diagnostics and limited effective therapies. Here we discuss PAD signs and symptoms, pathophysiological mechanisms, current management, and future disease targets and possible therapeutic treatments for PAD.

Endothelial Dysfunction and Inflammation

Endothelial Dysfunction and Inflammation
A Book

by Shauna Dauphinee,Aly Karsan

  • Publisher : Springer Science & Business Media
  • Release : 2010-09-24
  • Pages : 234
  • ISBN : 3034601689
  • Language : En, Es, Fr & De
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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.

Endothelium

Endothelium
Molecular Aspects of Metabolic Disorders

by Ayse Basak Engin,Atilla Engin

  • Publisher : CRC Press
  • Release : 2013-05-29
  • Pages : 468
  • ISBN : 1466582804
  • Language : En, Es, Fr & De
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The function and life span of endothelial cells have a large impact upon the quality and expectancy of an individual's life. During low perfusion, the adaptation of different cells to hypoxia precipitate the aggressive progression of diseases. Although the clinical studies have convincingly shown that endothelial dysfunction occurs whenever the biological functions or bioavailability of nitric oxide are impaired, in all these scenarios, the role of endothelial cell-destructive process cross-talk is yet poorly understood. This book focuses on the contribution of molecular mechanisms to endothelial dysfunction in related metabolic disorders.

Endothelium and Cardiovascular Diseases

Endothelium and Cardiovascular Diseases
Vascular Biology and Clinical Syndromes

by Protasio Lemos Da Luz,Peter Libby,Francisco Rafael Martins Laurindo,Antonio Carlos Palandri Chagas

  • Publisher : Academic Press
  • Release : 2018-02-03
  • Pages : 758
  • ISBN : 0128125519
  • Language : En, Es, Fr & De
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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

Vascular Aging: Facts and Factors

Vascular Aging: Facts and Factors
A Book

by Elisabet Vila,Francesc Jiménez-Altayó,Paula Dantas

  • Publisher : Frontiers E-books
  • Release : 2021
  • Pages : 329
  • ISBN : 2889190528
  • Language : En, Es, Fr & De
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The increasing mean age of the population in developed countries has turned out to be an economic and social problem. Cardiovascular disease has long been considered to be age related in terms of their onset and progression. As such, we can say that the increase in life expectancy goes in parallel with increased incidence of cardiovascular disease. With age, a number of changes occur in the vasculature altering the homeostasis of the irrigated organs promoting target organ damage. While different adaptive mechanisms to protect vessels against mild stress have been described, the aging process induces a progressive failure of protective mechanisms, leading to vascular changes and higher susceptibility to cardiovascular diseases. Indeed, vascular aging is exacerbated by coexisting cardiovascular risk factors, such as hypertension, metabolic syndrome and diabetes. Compelling evidence indicates that diminished endothelial relaxation and increase, decrease, or no change in contractile responses to several agonists is associated with aging. There is an increase of vasoconstrictor factors expression and a decrease of vasodilators. Morphologic changes include lumen diameter enlargement, wall thickening and alterations of matrix substances as increased collagen or decreased elastin deposition, ultimately leading to greater arterial stiffening (reduced compliance). Importantly, arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. Cellular and molecular mechanisms have also been documented. Senescence at the cellular level involves alterations in Ca2+ signaling and down regulation of anti-aging proteins. Both endothelial and smooth muscle cells change their number, morphology, function and their regenerative ability. Aging is also associated with a gradual loss of antioxidant defense mechanisms, a proinflammatory shift in the cytokine expression profile and a production of reactive oxygen species such as superoxide (O2-) that promotes the breakdown of nitric oxide. Nitric oxide and O2- interact to form peroxynitrite known to nitrosylate proteins affecting their physiological function. However, vascular wall proteins may also suffer from other potentially deleterious modifications as glycation (Maillard reaction) and glyco-oxidative reactions with increasing age, which could be linked to the age-associated changes in vascular function. Various strategies have shown benefit in preventing, delaying or attenuating vascular aging. For instance, a healthy lifestyle including low fat diet and/or exercise have a favorable effect. Nevertheless, it yet remains to be fully demonstrated whether vascular aging can be pharmacologically prevented. This Research Topic is intended to bring together research efforts to understand the causes and consequences of vascular aging and propose new therapeutic strategies for the management of vascular senescence.

THE PRO-INFLAMMATORY ROLE OF G-PROTEIN COUPLED RECEPTOR 4 IN AN ACIDIC MICROENVIRONMENT.

THE PRO-INFLAMMATORY ROLE OF G-PROTEIN COUPLED RECEPTOR 4 IN AN ACIDIC MICROENVIRONMENT.
A Book

by Elizabeth Krewson

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 206
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The endothelium of the microvascular system serves an ideal mediator between circulating blood and tissues in order to regulate systemic homeostasis. During vascular disease, the normal function and phenotype of endothelial cells is altered and leads to endothelial dysfunction. In turn, vascular disease disrupts blood flow to downstream tissues and leads to tissue hypoxia and acidification. Localized acidification commonly exists in inflammatory tissues due to altered glycolytic metabolism, hypoxia and insufficient tissue perfusion. How the body initially detects and responds to an acidic microenvironment is crucial for endothelial metabolism, cytoskeletal alterations, and cell survival. G-protein receptor 4 (GPR4) is a proton-sensing G-protein coupled receptor highly expressed in vascular endothelial cells. GPR4 can initiate various signaling pathways based on its activation by extracellular protons. This dissertation focuses on acidosis-mediated GPR4 signaling and its role as a positive regulator of inflammation using in vitro and in vivo models. We microscopically evaluated permeability and cytoskeletal components, including fibrous actin rearrangements and vascular endothelial-cadherin alterations under acidic stress conditions in endothelial cells. In vitro data demonstrated that GPR4 is a key mediator for endothelial permeability by targeting one of the G-protein signaling pathways, G12/13, to initiate a cascade in order to regulate endothelial permeability. Additionally, we employed a widely established tourniquet-based hindlimb ischemia murine model to initiate a localized ischemic milieu followed by a reperfusion (release of cuff) event. To evaluate the biological role associated with GPR4, we utilized a genetic GPR4 knockout mouse and a small molecule inhibitor to abolish GPR4 signaling. Our immunohistochemical data show less serum immunoglobulin G leakage and inflammatory response in the GPR4 knockout mice compared to the wild type mice. These and other data suggest GPR4 deficiency reduces hindlimb edema, exudate quantity, and leukocyte migration to the loose connective tissue due to endothelial permeability alterations mediated by GPR4 signaling. This work highlights many GPR4-dependent properties from promoting endothelial permeability for leukocyte trafficking to eliciting a cytoskeletal response by the G12/13 G-protein signaling pathway cascade. Understanding how vascular endothelial cells sense and respond to an acidic microenvironment is critical for identifying therapeutic targets for cancers, cardiovascular, and ischemic diseases.

Regulation of Endothelial Barrier Function

Regulation of Endothelial Barrier Function
A Book

by Sarah Y. Yuan,Robert R. Rigor

  • Publisher : Morgan & Claypool Publishers
  • Release : 2010-09-30
  • Pages : 143
  • ISBN : 1615041206
  • Language : En, Es, Fr & De
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The vascular endothelium lining the inner surface of blood vessels serves as the first interface for circulating blood components to interact with cells of the vascular wall and surrounding extravascular tissues. In addition to regulating blood delivery and perfusion, a major function of vascular endothelia, especially those in exchange microvessels (capillaries and postcapillary venules), is to provide a semipermeable barrier that controls blood-tissue exchange of fluids, nutrients, and metabolic wastes while preventing pathogens or harmful materials in the circulation from entering into tissues. During host defense against infection or tissue injury, endothelial barrier dysfunction occurs as a consequence as well as cause of inflammatory responses. Plasma leakage disturbs fluid homeostasis and impairs tissue oxygenation, a pathophysiological process contributing to multiple organ dysfunction associated with trauma, infection, metabolic disorder, and other forms of disease. In this book, we provide an updated overview of microvascular endothelial barrier structure and function in health and disease. The discussion is initiated with the basic physiological principles of fluid and solute transport across microvascular endothelium, followed by detailed information on endothelial cell-cell and cell-matrix interactions and the experimental techniques that are employed to measure endothelial permeability. Further discussion focuses on the signaling and molecular mechanisms of endothelial barrier responses to various stimulations or drugs, as well as their relevance to several common clinical conditions. Taken together, this book provides a comprehensive analysis of microvascular endothelial cell and molecular pathophysiology. Such information will assist scientists and clinicians in advanced basic and clinical research for improved health care. Table of Contents: Acknowledgments / Introduction / Structure and Function of Exchange Microvessels / Methods for Measuring Permeability / The Endothelial Barrier / Signaling Mechanisms in the Regulation of Endothelial Permeability / Endothelial Barrier Protectors / Pathophysiology and Clinical Relevance / Conclusion / References

Mechanisms of Vascular Disease

Mechanisms of Vascular Disease
Divergent Roles for Suppressor of Cytokine Signaling 3 in Angiotensin II-induced Vascular Dysfunction

by Ying Li,University of Iowa. Department of Pharmacology

  • Publisher : Unknown Publisher
  • Release : 2014
  • Pages : 166
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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To investigate potential mechanisms underlying divergent results when studying effects of local versus systemic effects of Ang II, we performed bone marrow transplantation followed by infusion of vehicle or Ang II for two weeks. Lethally irradiated WT (CD45.1) mice reconstituted with SOCS3+/- bone marrow were protected from Ang II-induced endothelial dysfunction (P

Textbook of Vascular Medicine

Textbook of Vascular Medicine
A Book

by Rhian M. Touyz,Christian Delles

  • Publisher : Springer
  • Release : 2019-08-02
  • Pages : 503
  • ISBN : 3030164810
  • Language : En, Es, Fr & De
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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.

Endothelial Signaling in Development and Disease

Endothelial Signaling in Development and Disease
A Book

by Mirko HH Schmidt,Stefan Liebner

  • Publisher : Springer
  • Release : 2015-10-08
  • Pages : 401
  • ISBN : 1493929070
  • Language : En, Es, Fr & De
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This book surveys healthy and diseased vascular systems in a multitude of model organisms and systems. It explores a plethora of functions, characteristics, and pathologies of the vascular system such as angiogenesis, fibroblast growth factor signaling, lymphangiogenesis, junctional signaling, the extracellular matrix, vascular permeability, leukocyte extravasation, axon guidance factors, the angiopoietin system, and chronic obstructive lung disease. Following a preface from leading researcher Dr. Holger Gerhardt, the text is divided into three sections- the first examining the development of the vascular system in a variety of contexts, the second delving into its homeostatic characteristics, and the third discussing its pathophysiologies. The sixteen chapters, which represent international clinical and research perspectives, highlight the importance of molecular and signaling pathways for translational basic science and clinical medicine. Additionally, the text explores new and exciting fields in vascular biology research. Comprehensive in both content and approach, Vascular Signaling in Health and Disease is ideal for graduate students, researchers, and clinicians interested in vascular biology, pneumology, and molecular biology.

Endothelial Dysfunction During Inflammation and Alloimmunity

Endothelial Dysfunction During Inflammation and Alloimmunity
A Book

by Olaf Penack,Thomas Luft

  • Publisher : Frontiers Media SA
  • Release : 2019-04-09
  • Pages : 126
  • ISBN : 2889458261
  • Language : En, Es, Fr & De
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Endothelial cells form the inner lining of blood and lymphatic vessels and they have frequent interactions with immune cells as well as foreign agents. Endothelial function is crucially involved in physiologic immunity at different stages including recruitment of leukocytes, angiogenesis and tissue repair. Endothelial dysfunction is a not well-defined term, it is widely used to describe the non-physiologic activity of endothelial cells. It has been suggested that endothelial dysfunction plays a role in a variety of human diseases, such as arteriosclerosis, cancer, autoimmunity and sepsis. More recently, a role of lymphatic endothelial cells as well as vascular endothelial cells in the pathophysiology of inflammation and allo-immune reactions has been suggested. Development of novel therapeutic approaches to normalize endothelial dysfunction is currently an unmet medical need. Until now, the cellular and molecular mechanisms of mutual influences between endothelial dysfunction and human diseases remain largely unexplored, constituting a frontier hindering the development of new therapies. This Research Topic aims to build a forum for a wide range of scientific studies in the fields of endothelial dysfunction during inflammatory diseases and transplantation.

Endothelium

Endothelium
A Book

by Anonim

  • Publisher : Academic Press
  • Release : 2016-07-20
  • Pages : 462
  • ISBN : 0128044152
  • Language : En, Es, Fr & De
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Endothelium, the new volume in the Advances in Pharmacology series, presents readers with a variety of chapters that cover various endothelium-derived mediators and their changes with gender, and during vascular development, senescence, and hypertensive disorders. Topics include endothelium, nitric oxide, gap junctions, potassium channels, endothelin, vascular development, vascular permeability, gender, aging, and preeclampsia. With contributions from the best authors in the field, the volume is an essential resource for pharmacologists, immunologists, and biochemists alike. Contains contributions from the best authors in the field Provides an essential resource for pharmacologists, immunologists, and biochemists Covers endothelium-derived mediators and their changes

Cardiovascular Biology

Cardiovascular Biology
Endothelial Cell in Health and Hypertension

by J. F. Stoltz

  • Publisher : IOS Press
  • Release : 2007
  • Pages : 211
  • ISBN : 9781586037758
  • Language : En, Es, Fr & De
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Vascular endothelial plays a significant role in regulating blood flow, and endothelial cells (EC) have highly active metabolic functions. This volume focuses on Vascular Endothelium, NO and Hypertension and is a continuum of the volumes on Mechanobiology of Cartilage and Chondrocyte.

The Role of AMP-activated Protein Kinase in Endothelial VEGF Signalling

The Role of AMP-activated Protein Kinase in Endothelial VEGF Signalling
A Book

by James Anthony Reihill

  • Publisher : Unknown Publisher
  • Release : 2009
  • Pages : 278
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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The endothelium acts to maintain vascular homeostasis, including the regulation of vascular tone, blood fluidity and coagulation. Endothelial dysfunction, a condition largely characterised by reduced NO bioavailability, is an important feature associated with the aetiology of several pathophysiological disorders including type 2 diabetes and cardiovascular disease. AMPK is the downstream component of a protein kinase cascade important in the regulation of cellular and whole body metabolism. AMPK has been demonstrated to mediate a number of physiological responses in the endothelium, including the stimulation of eNOS phosphorylation and NO synthesis; and as such AMPK represents a therapeutic target in the dysfunctional endothelium. VEGF has been established as the prime angiogenic molecule during development, adult physiology and pathology. VEGF stimulates NO production, proposed to be a result of phosphorylation of Ser-1177 on eNOS, a residue also phosphorylated upon AMPK activation in cultured endothelial cells. The present study, utilising HAEC as a model, provides the first demonstration that AMPK is activated by physiological concentrations of VEGF; and furthermore, partially mediates VEGF-stimulated phosphorylation of eNOS on Ser-1177 and subsequent NO production. In addition, the present investigation demonstrates that the upstream AMPK kinase CaMKK is responsible for these VEGF-mediated effects. VEGF is known to increase intracellular calcium levels in endothelial cells via the generation of DAG and IP3. DAG increases Ca2 influx through a family of non-selective cation channels, whereas IP3 promotes the release of Ca2 from intracellular stores. High potassium-induced depolarisation, which reduces the driving force for Ca2+ entry through non-selective cation channels in endothelial cells, abolished VEGF-mediated AMPK activation, whereas the IP3 receptor blocker 2-APB was without effect. Exposure of HAEC to a DAG mimetic (OAG) also stimulated AMPK, an effect which was sensitive to the CaMKK inhibitor STO-609 and high potassium induced depolarization. The functional effects of VEGF-stimulated AMPK were also assessed in HAEC. Ablation of AMPK abrogated VEGF-stimulated HAEC migration and proliferation, two key features of the angiogenic process. While AMPK was necessary for VEGF-stimulated endothelial cell proliferation direct activation of the kinase was insufficient to induce this process. AICAR-stimulated AMPK activation has been demonstrated to stimulate fatty acid oxidation in endothelial cells. However, exposure of HAEC to VEGF did not alter fatty acid oxidation in the present study. Together, the current investigation suggests that a VEGF-Ca2+-CaMKK-AMPK-eNOS-NO pathway is present in HAEC, and furthermore, that AMPK is required, albeit insufficient, for the VEGF-stimulated angiogenic response.

Oxidative Stress Revisited - Major Role in Vascular Diseases

Oxidative Stress Revisited - Major Role in Vascular Diseases
A Book

by Cristina M. Sena,Raquel Seiça,George Perry

  • Publisher : Frontiers Media SA
  • Release : 2019-10-21
  • Pages : 329
  • ISBN : 2889630587
  • Language : En, Es, Fr & De
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Oxidative stress is an underlying factor in health and disease. Reactive oxygen species are produced as a result of normal cellular metabolism. The subsequent altered redox state between the formation and the neutralization of pro-oxidants results in their increased levels and therefore leads to cellular damage. Different research disciplines have increased our knowledge of the importance of this cell redox status and the recognition of oxidative stress as a process with implications for many pathophysiological states. Genetic and environmental factors, nutrition and lifestyle may indicate a pro-oxidative and pro-inflammatory state, linked to alterations in cellular structure and function. Oxidative stress emerges as a common, unifying factor in several conditions including diabetes and cardiovascular diseases. This eBook aims to provide novel data regarding the role played by oxidative stress and inflammation in the development of chronic diseases and the different classes of therapeutics from the bench to the clinic, stressing the awareness of these concepts for the treatment of disease. In addition, articles addressing an overview of the role of oxidative stress in vascular diseases reviewing some current concepts indicating that oxidative stress and inflammation are key mechanisms linking vascular diseases and current state-of-the-art approaches to monitor, prevent and inhibit oxidative stress will be highlighted. There is a close relation between oxidative stress, inflammation and cardiovascular diseases. Despite the great amount of investigation carried out in the field, there are still uncertainties about the mechanisms by which free radicals can modify tissues such as perivascular adipose tissue that ultimately will reflect on vascular function. This eBook will focus on articles that can explore and identify these mechanisms. Concurrent with this understanding of oxidative stress milieu, it is necessary to recognize the need for new pharmacological tools effective in restoring oxidative balance. The abundance of new information and the paradigm shift in our understanding of how antioxidants and other redox-active drugs work in a wide variety of vascular diseases will be specifically highlighted. This eBook will provide a comprehensive, up-to-date source of information on the design and mechanistic, pharmacological, and medicinal aspects of redox-active therapeutics. Finally, a unique feature of the eBook is to provide a way to foster an enthralling discussion revisiting old paradigms and finding new solutions for the treatment of vascular diseases. The topic will include original research articles, hypotheses, perspectives and (mini)reviews from experts in the field. The next decade shows promise for the translation of this body of knowledge to novel human therapeutics and this eBook will enable to increment our knowledge in this field.