Endothelial Signaling in Vascular Dysfunction and Disease

Endothelial Signaling in Vascular Dysfunction and Disease
Author: Shampa Chatterjee
Publsiher: Academic Press
Total Pages: 274
Release: 2021-01-20
ISBN 10: 0128163828
ISBN 13: 9780128163825
Language: EN, FR, DE, ES & NL

Endothelial Signaling in Vascular Dysfunction and Disease Book Review:

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

The Endothelium

The Endothelium
Author: Michel Félétou
Publsiher: Morgan & Claypool Publishers
Total Pages: 281
Release: 2011
ISBN 10: 1615041230
ISBN 13: 9781615041237
Language: EN, FR, DE, ES & NL

The Endothelium Book Review:

"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. "--Publisher.

Endothelium and Cardiovascular Diseases

Endothelium and Cardiovascular Diseases
Author: Protasio Lemos Da Luz,Peter Libby,Francisco Rafael Martins Laurindo,Antonio Carlos Palandri Chagas
Publsiher: Academic Press
Total Pages: 758
Release: 2018-02-03
ISBN 10: 0128125519
ISBN 13: 9780128125519
Language: EN, FR, DE, ES & NL

Endothelium and Cardiovascular Diseases Book Review:

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

Mechanisms of Vascular Disease

Mechanisms of Vascular Disease
Author: Robert Fitridge,Matthew Thompson
Publsiher: University of Adelaide Press
Total Pages: 587
Release: 2011-01-01
ISBN 10: 1922064009
ISBN 13: 9781922064004
Language: EN, FR, DE, ES & NL

Mechanisms of Vascular Disease Book Review:

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.

Endothelial Dysfunction

Endothelial Dysfunction
Author: Helena Lenasi
Publsiher: BoD – Books on Demand
Total Pages: 430
Release: 2018-10-24
ISBN 10: 1789842530
ISBN 13: 9781789842531
Language: EN, FR, DE, ES & NL

Endothelial Dysfunction Book Review:

The endothelium enables communication between blood and tissues and is actively involved in cardiovascular homeostasis. Endothelial dysfunction has been recognized as an early step in the development of cardiovascular diseases: respectively, endothelium represents a potential therapeutic niche with multiple targets. The purpose of the book is to point out some recent findings of endothelial physiology and pathophysiology emphasizing various aspects of endothelial dysfunction connected to the body's internal and external environment. While basic features of the endothelium are presented in an introductory chapter, the authors of the following 17 chapters have provided extensive insight into some selected topics of endothelial (dys)function. The book would hopefully be useful for anyone interested in recapitulating endothelial (patho)physiology and expanding knowledge of molecular mechanisms involved in endothelial dysfunction, relevant also for further clinical investigations.

TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades

TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades
Author: Wolfgang B. Liedtke, MD, PH.D.
Publsiher: CRC Press
Total Pages: 467
Release: 2006-09-29
ISBN 10: 1420005847
ISBN 13: 9781420005844
Language: EN, FR, DE, ES & NL

TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Book Review:

Since the first TRP ion channel was discovered in Drosophila melanogaster in 1989, the progress made in this area of signaling research has yielded findings that offer the potential to dramatically impact human health and wellness. Involved in gateway activity for all five of our senses, TRP channels have been shown to respond to a wide range of stimuli from both within and outside the cell body. How we sense heat and cold, how we taste food, how eggs are fertilized, how the heart expands and contracts is each dependent on the function of these channels. While no single book could possibly cover all the research being undertaken, TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades presents the most advanced compilation of work in this area to date. All 31 chapters are written by international pioneers working at the vanguard of TRP ion channel research. They explain much about the pivotal function and behavior of these channels, which are most exquisitely tuned to their specific tasks, and delve into how researchers are putting this knowledge to use in the development of novel pharmaceuticals, which may well prove effective in ameliorating treatment-resistant conditions including cancer, heart disease, inflammation, and immune system dysfunctions. Individual chapters shed light on selected topics of interest in the TRP arena, such as signal transduction in axonal path-finding, and in vascular, renal, and auditory functions, as well as pain. The text also covers subjects as diverse as mating and fertilization, inflammatory pain, and mechanisms of pheromone detection in mammals. While the book presents much new insight and explores findings that will be of interest to those involved with advanced research, it also includes significant background material for those looking to familiarize themselves with this exceptionally promising path of inquiry.

Molecular Biology of the Cell

Molecular Biology of the Cell
Author: Bruce Alberts
Publsiher: Unknown
Total Pages: 135
Release: 2004
ISBN 10: 9780815332183
ISBN 13: 0815332181
Language: EN, FR, DE, ES & NL

Molecular Biology of the Cell Book Review:

Pediatric Hypertension

Pediatric Hypertension
Author: Joseph Flynn,Julie R. Ingelfinger,Ronald J. Portman
Publsiher: Springer Science & Business Media
Total Pages: 600
Release: 2013-06-26
ISBN 10: 1627034900
ISBN 13: 9781627034906
Language: EN, FR, DE, ES & NL

Pediatric Hypertension Book Review:

The field of pediatric hypertension has undergone important changes in the time since the second edition of Pediatric Hypertension published. Much new information on hypertension in the young has become available. Previous chapters have been fully revised and new chapters have been added to cover important topics of recent interest such as consensus recommendations, the prevalence of hypertension in the young due to the obesity epidemic, studies of antihypertensive agents, and ambulatory blood pressure monitoring. Pediatric Hypertension, Third Edition is a comprehensive volume featuring 38 chapters covering the breadth of the current knowledge. It is divided into four sections: Regulation of Blood Pressure in Children; Assessment of Blood Pressure in Children: Measurement, Normative Data, Epidemiology; and Hypertension in Children: Predictors, Risk Factors, and Special Populations; Evaluation and Management of Pediatric Hypertension. Filled with the most up-to-date information, Pediatric Hypertension, Third Edition is an invaluable resource for clinicians and researchers interested in childhood hypertension.

MYELOPEROXIDASE INDUCES ENDOTHELIAL DYSFUNCTION VIA ACTIVATION OF THE CALCIUM DEPENDENT PROTEASE CALPAIN

MYELOPEROXIDASE INDUCES ENDOTHELIAL DYSFUNCTION VIA ACTIVATION OF THE CALCIUM DEPENDENT PROTEASE CALPAIN
Author: Zienab Etwebi
Publsiher: Unknown
Total Pages: 104
Release: 2018
ISBN 10: 1928374650XXX
ISBN 13: OCLC:1280138319
Language: EN, FR, DE, ES & NL

MYELOPEROXIDASE INDUCES ENDOTHELIAL DYSFUNCTION VIA ACTIVATION OF THE CALCIUM DEPENDENT PROTEASE CALPAIN Book Review:

Cardiovascular disease and the associated endothelial dysfunction are characterized by leukocyte activation, decrease endothelial nitric oxide synthase (eNOS) activity, and increased endothelial cell adhesion molecules expression. This leads to the release of myeloperoxidase (MPO) by activated neutrophils and monocytes. MPO is a peroxidase enzyme that plays an important role in innate immune host defense, however it has been shown to play a pathogenic role in cardiovascular disease, mainly by causing endothelial dysfunction. The molecular mechanisms through which MPO induces endothelial damage are not fully understood. Calpains are a family of calcium-dependent proteases. Two calpain isoforms, μ- and m-calpain, are expressed in the vascular wall, including endothelial cells. Activation of calpains has been recently implicated in inflammatory disorders of the vasculature. The goal of this study was to test the hypothesis of a role for calpains in the molecular mechanism(s) through which MPO causes endothelial dysfunction and vascular inflammation. To explore if MPO activates calpain and to identify the calpain isoform(s) involved, we first studied the effects of MPO treatment on calpain activity in mouse lung microvascular endothelial cells (MMVEC). MMVECs were stimulated with 10 nmol/L MPO for 60, 120, 180, and 240 min. Using a fluorescent calpain activity assay, we found that MPO time dependently activates calpain in endothelial cells, with peak activity reached within 180 min. Using immunoblot analysis techniques we demonstrated that the calpain isoform targeted by MPO is μ-calpain. Interestingly, using a biotin switch assay,10 nmol/L MPO appears to activate the μ-calpain isoform via denitrosylation of its C-terminus domain. Using MMVECs, we studied the effects of the MPO/μ-calpain signaling on endothelial dysfunction. MMVECs were stimulated with 10 nmol/L MPO for 180 min. Expression levels of Protein Phosphatase 2 (PP2A), total 5' AMP-activated protein kinase (AMPK), Thr172 phospho-AMPK, total endothelial nitric oxide synthase (eNOS),Ser1177 phospho-eNOS, total protein kinase B (AKT), Ser473 phospho AKT, Adiponectin receptor 1 (AdipoR1), and Adiponectin receptor 2 (AdipoR2), were measured by immunoblot analysis. Interestingly, MPO impaired Thr172AMPK, Ser1177eNOS, but not Ser 473 AKT phosphorylation in a calpain dependent manner. On the other hand, MPO significantly increased the expression levels of PP2A. Inhibition of PP2A with okadiak acid decreased the phosphorylation levels of AMPK, and eNOS, indicating that PP2A is a downstream target of the MPO/calpain system. MPO treatment significantly increased the expression of vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells. Pharmacological inhibition of calpain activity attenuated expression of VCAM-1. MPO also decreased protein levels of AdipoR1, and AdipoR2 in a calpain dependent manner. The treatment of MMVEC with adiponectin in the presence of MPO was not able to restore AdipoR2 expression levels. Using genetically modified mice, we found evidence of reduced leukocyte adhesion to the aortic endothelium in response to MPO in μ-calpain deficient mice, compared to wild-type mice . These effects appears to be attributed to the endothelial calpain, since incubating wild type aortas with calpain deficient leukocytes did not reduce leukocyte adhesion to the endothelium. The data in this study first establish a role for calpain in the endothelial dysfunction and vascular inflammation of MPO, with MPO activating the μ-calpain isoform via denitrosylation. Our data also report that increased calpain activity downregulats the expression of a number of signaling molecules important for endothelial cell function. This study may provide the MPO/calpain/PP2A signaling pathway as a novel pharmacological targets for the treatment of inflammation-driven vascular disorders.

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
Author: Carlos Alonso Escudero,Fernanda Regina Giachini,Carlos Galaviz-Hernandez,Alicia E. Damiano
Publsiher: Frontiers Media SA
Total Pages: 136
Release: 2019-11-22
ISBN 10: 2889632016
ISBN 13: 9782889632015
Language: EN, FR, DE, ES & NL

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

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.

Regulation of Endothelial Barrier Function

Regulation of Endothelial Barrier Function
Author: Sarah Y. Yuan,Robert R. Rigor
Publsiher: Biota Publishing
Total Pages: 146
Release: 2011-02-01
ISBN 10: 1615041214
ISBN 13: 9781615041213
Language: EN, FR, DE, ES & NL

Regulation of Endothelial Barrier Function Book Review:

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.

Measuring Oxidants and Oxidative Stress in Biological Systems

Measuring Oxidants and Oxidative Stress in Biological Systems
Author: Lawrence J. Berliner,Narasimham L. Parinandi
Publsiher: Springer Nature
Total Pages: 237
Release: 2020-08-08
ISBN 10: 303047318X
ISBN 13: 9783030473181
Language: EN, FR, DE, ES & NL

Measuring Oxidants and Oxidative Stress in Biological Systems Book Review:

This book describes the methods of analysis and determination of oxidants and oxidative stress in biological systems. Reviews and protocols on select methods of analysis of ROS, RNS, oxygen, redox status, and oxidative stress in biological systems are described in detail. It is an essential resource for both novices and experts in the field of oxidant and oxidative stress biology.

Regulation of Vascular Smooth Muscle Function

Regulation of Vascular Smooth Muscle Function
Author: Raouf A. Khalil
Publsiher: Morgan & Claypool Publishers
Total Pages: 62
Release: 2010
ISBN 10: 161504180X
ISBN 13: 9781615041800
Language: EN, FR, DE, ES & NL

Regulation of Vascular Smooth Muscle Function Book Review:

In book the role of Ca2+ and other signaling pathways of Vascular smooth muscle (VSM) contraction will be discussed. VSM contraction plays an important role in the regulation of vascular resistance and blood pressure, and its dysregulation may lead to vascular diseases such as hypertension and coronary artery disease. Under physiological conditions, agonist activation of VSM results in an initial phasic contraction followed by a tonic contraction. The initial agonist-induced contraction is generally believed to be due to Ca2+ release from the intracellular stores. Although VSM is unique in that it can sustain contraction with minimal energy expense, the mechanisms involved in the maintained VSM contraction are not clearly understood.

Endothelial Dysfunction and Inflammation

Endothelial Dysfunction and Inflammation
Author: Shauna Dauphinee,Aly Karsan
Publsiher: Springer Science & Business Media
Total Pages: 234
Release: 2010-09-24
ISBN 10: 3034601689
ISBN 13: 9783034601689
Language: EN, FR, DE, ES & NL

Endothelial Dysfunction and Inflammation Book Review:

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.

Vasculitis In Practice

Vasculitis In Practice
Author: Reem Mohammed
Publsiher: BoD – Books on Demand
Total Pages: 112
Release: 2018-09-19
ISBN 10: 1789236983
ISBN 13: 9781789236989
Language: EN, FR, DE, ES & NL

Vasculitis In Practice Book Review:

"Vasculitis" describes an inflammatory process that involves the blood vessels and contributes to vascular damage. Autoimmunity, infections, drugs, and malignancies have been considered among potential etio-pathogenic factors. In vasculitis, the inflammation might develop in either a systemic or an organ-specific form and might exist as an independent pathology "primary vasculitis" or as a presentation of an existing primary pathology, that is, "secondary vasculitis". This book Vasculitis In Practice-An Update on Special Situations - Clinical and Therapeutic Considerations unlike many publications in the field, uses a different evidence-based approach to organ-specific vascular inflammatory diseases. The authors highlighted the unmet needs from the 1994 Chapel Hill Consensus Conference introducing the latest clinically relevant definitions for the different forms of vasculitis revised in 2012. The identification, classification, and management of kidney disease with different types of vasculitis with an evidence-based update on proposed therapeutic strategies are presented in this publication.

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
Author: Steven Garfield Denniss
Publsiher: Unknown
Total Pages: 216
Release: 2011
ISBN 10: 1928374650XXX
ISBN 13: OCLC:926096791
Language: EN, FR, DE, ES & NL

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

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 EDCF signaling activity were affected by these BSO-induced perturbations. Conclusions and Perspective: In the CCA of animals at the early pathological stages of either essential hypertension (young adult SHR) or normotensive aging (Aging SD rats), endothelial vasomotor dysfunction can be caused solely by over-active EDCF signaling, apparently disconnected from changes in NO bioavailability or oxidative stress. While NO and ROS may act, respectively, as negative and positive modulators of the established COX-PG-TP receptor-RhoA-ROCK cell-signaling axis mediating endothelium-dependent contractile activity, these factors do not appear to be essential to the mechanism(s) underlying the development of over-active EDCF signaling. Further elucidation of the cellular-molecular causes of over-active EDCF signaling, and its patho-biological consequences, in the SHR-WKY and Adult-Aging SD rat CCA models of EDCF activity established and hemodynamically characterized in this thesis, may help to identify new or more effective targets to be used in prevention or treatment strategies to combat the pathogenesis of CVD.

Endothelial Signaling in Development and Disease

Endothelial Signaling in Development and Disease
Author: Mirko HH Schmidt,Stefan Liebner
Publsiher: Springer
Total Pages: 401
Release: 2015-10-08
ISBN 10: 1493929070
ISBN 13: 9781493929078
Language: EN, FR, DE, ES & NL

Endothelial Signaling in Development and Disease Book Review:

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.

Mechanisms of Vascular Disease

Mechanisms of Vascular Disease
Author: Ying Li,University of Iowa. Department of Pharmacology
Publsiher: Unknown
Total Pages: 166
Release: 2014
ISBN 10: 1928374650XXX
ISBN 13: OCLC:903061899
Language: EN, FR, DE, ES & NL

Mechanisms of Vascular Disease Book Review:

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

Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension

Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension
Author: Toshio Nakanishi,H. Scott Baldwin,Jeffrey R. Fineman,Hiroyuki Yamagishi
Publsiher: Springer Nature
Total Pages: 405
Release: 2020-02-28
ISBN 10: 9811511853
ISBN 13: 9789811511851
Language: EN, FR, DE, ES & NL

Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension Book Review:

This open access book focuses on the molecular mechanism of congenital heart disease and pulmonary hypertension, offering new insights into the development of pulmonary circulation and the ductus arteriosus. It describes in detail the molecular mechanisms involved in the development and morphogenesis of the heart, lungs and ductus arteriosus, covering a range of topics such as gene functions, growth factors, transcription factors and cellular interactions, as well as stem cell engineering technologies. The book also presents recent advances in our understanding of the molecular mechanism of lung development, pulmonary hypertension and molecular regulation of the ductus arteriosus. As such, it is an ideal resource for physicians, scientists and investigators interested in the latest findings on the origins of congenital heart disease and potential future therapies involving pulmonary circulation/hypertension and the ductus arteriosus.

Peripheral Arterial Disease

Peripheral Arterial Disease
Author: Christopher G. Kevil,Shyamal C. Bir,Christopher B. Pattillo
Publsiher: Biota Publishing
Total Pages: 82
Release: 2013-08-01
ISBN 10: 1615045996
ISBN 13: 9781615045990
Language: EN, FR, DE, ES & NL

Peripheral Arterial Disease Book Review:

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.