The Role Of Inhibitor 1 And Heat Shock Protein 20 In Cardiac Pathophysiology
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The Role Of Inhibitor 1 And Heat Shock Protein 20 In Cardiac Pathophysiology
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Author : Persoulla Nicolaou
language : en
Publisher:
Release Date : 2008
The Role Of Inhibitor 1 And Heat Shock Protein 20 In Cardiac Pathophysiology written by Persoulla Nicolaou and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
Cardiovascular disease, which remains the leading cause of mortality in the Western world, is manifested in contractile dysfunction, myocardial infarction and arrhythmias. These detrimental effects are partially attributed to impaired Ca cycling and cell death. Since calsequestrin (CSQ) and inhibitor-1 (I-1) are key regulators of Ca cycling and the anti-apoptotic small heat shock protein 20 (Hsp20) is an important mediator of cardioprotection, this dissertation sought to gain further insights into the role of these proteins in cardiac pathophysiology. CSQ is a crucial regulator of Ca load in the sarcoplasmic reticulum and the Ca-release channel, the ryanodine receptor. Interestingly, human CSQ null mutations have been associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). To further address the significance of CSQ and CSQ null mutations, this dissertation attempted to generate a mouse model with ablation of CSQ. I-1 and its phosphorylation at Thr35 are important mediators of the heart's beta-adrenergic responses. To address any potential beneficial effects of enhanced I-1 activity in the adult heart, a mouse model with inducible expression of active I-1 (T35D) was generated. Active I-1 expression significantly enhanced contractility, associated with preferential phospholamban (PLN) and myosin light chain 2a phosphorylation. Upon ischemia/reperfusion (I/R), active I-1 augmented contractile function, associated with increased pThr17-PLN phosphorylation. Further examination revealed that the infarct region and apoptotic as well as necrotic injury were significantly attenuated by enhanced I-1 activity, associated with suppression of the endoplasmic reticulum stress response. These findings indicate that active I-1 may represent a potential therapeutic strategy in myocardial infarction. Hsp20 and its phosphorylation at Ser16 protect cardiomyocytes against apoptosis. To determine whether genetic variants exist in human Hsp20, which may modify these beneficial effects, the Hsp20 gene was sequenced in dilated cardiomyopathic patients and individuals with no heart disease. A C59T substitution was identified in Hsp20 in one patient and three individuals without heart disease. This mutation changes a conserved proline residue into leucine at position 20 (P20L), resulting in secondary structural alterations. The significance of this variant was assessed by subjecting cardiomyocytes, infected with Ad. GFP, Ad. WT-Hsp20 and Ad. P20L-Hsp20, to simulated ischemia/reperfusion. Expression of WT-Hsp20 significantly attenuated apoptotic injury, while the P20L-Hsp20 mutant showed no protection. This was associated with the mutant's diminished phosphorylation at Ser16. Furthermore, stimulation of cardiomyocytes with isoproterenol and protein kinase A-dependent phosphorylation in vitro confirmed the impaired ability of the mutant Hsp20 to become phosphorylated at Ser16. These findings indicate that the P20L substitution in Hsp20, may adversely affect the ability of human carriers to cope with cellular stress. Furthermore, a C29T transversion was identified exclusively in black cardiomyopathic males. This mutation results in substitution of serine at position 10 to phenylalanine (S10F), with similar structural alterations to the P20L mutant, suggesting that the S10F substitution may also have adverse effects on Hsp20's cardioprotective properties. Collectively, this dissertation provides novel insights into the role of these key regulatory proteins in the diseased myocardium, further illuminating the molecular and genetic defects, associated with cardiovascular disease, which may provide potential therapeutic strategies to alleviate its detriment.
Introduction To Translational Cardiovascular Research
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Author : Dennis V. Cokkinos
language : en
Publisher: Springer
Release Date : 2014-11-06
Introduction To Translational Cardiovascular Research written by Dennis V. Cokkinos and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-11-06 with Medical categories.
The term “Translational Research” reflects today’s integration of basic research (“bench”) findings with the clinical practice of medicine, and in a wider scope the application of results from the individual patient (“bedside”) to entire populations for the improvement of public health. This book offers future researchers a stimulus in many aspects of cardiovascular research, so as to promote their interest in future fields of cardiovascular disease, diagnosis and treatment. Introduction to Translational Cardiovascular Research discusses the fundamental and important aspects of the topic. It describes the renin-angiotensin-aldosterone system, the beta adrenergic receptors and the hypothalamic-pituitary-adrenal axis, while covering genetic polymorphisms both generally and specifically as regards the vascular endothelium and the use of microRNAs. As such, this book will be relevant to young physicians, nurses and other scientists engaged in the clinical cardiovascular field who want to added research-oriented dimension to their efforts towards better understanding and practicing of medicine. It also aims to attract young basic researchers who want to develop a better comprehension of the organism as a whole, man or animal, that they are investigating.
Basic Cardiovascular Physiology
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Author : Pasquale Pagliaro
language : en
Publisher: CRC Press
Release Date : 2022-09-01
Basic Cardiovascular Physiology written by Pasquale Pagliaro and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-09-01 with Medical categories.
This book focuses on established cardiovascular principles and highlights some of the progress achieved by recent research in the cardiovascular field. The authors report the basic concepts related to the functioning of the cardiovascular system necessary for medical students to understand. To foster learning, in each chapter the fundamental points are highlighted in italics and/or bold. In addition, we have added boxes that contain some more detailed information about physiological mechanisms or clinical aspects are analyzed and described in greater detail. The book describes the structure and function of the heart and vascular system for the reader to understand how the cardiovascular system responds in both health and disease. The book conveys a unified vision of the function of the heart and the vascular system, explaining the complexity of the system that goes far beyond the integrated connection between preload, afterload and cardiac contractility. The endothelium covers the internal part of the whole cardiovascular system; therefore, endothelial physiology is treated in several chapters. Given the importance of coronary circulation in cardiac pathophysiology, this special circulation is described in detail and enriched with the most up-to-date information. Several paragraphs and boxes on clinical implications are dedicated to the principles of electrophysiology and the electrocardiogram. A space is also dedicated to myocardial ischemia/reperfusion injury and cardioprotective procedures. The book is written in a linear and simple language without compromising the scientific rigor of the various topics covered.
Heat Shock Proteins And Whole Body Physiology
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Author : Alexzander A. A. Asea
language : en
Publisher: Springer Science & Business Media
Release Date : 2009-12-10
Heat Shock Proteins And Whole Body Physiology written by Alexzander A. A. Asea and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-12-10 with Medical categories.
Heat Shock Proteins and Whole Body Physiology is an exciting new book in the Heat Shock Proteins series which provides the most up-to-date review on novel mechanisms insights into the important role played by heat shock proteins in human physiology. Written by leaders in the field of heat shock protein exercise physiology, neuroscience and aging, the chapters systematically and in a step wise fashion takes the reader through the fascinating mechanisms by which heat shock proteins modulate human disease and pathophysiology and provides answers as to its biological significance to the host. Section I, introduces the readers to the role played by heat shock proteins in various diseases and disorders (Heat Shock Proteins and Disease). Section II, addresses the role heat shock proteins play in psychological disorders including post traumatic stress disorders and learning (Heat Shock Proteins and Psychological Stress). Section III, present a detailed review of the role played by heat shock proteins in exercise physiology (Heat Shock Proteins and Exercise Physiology). This book is a must read for heat shock protein researchers, graduate and postgraduate fellows in the field of Medicine in general and specialities in Excersie Physiology, Neuroscience, Immunology, Aging and Pathology.
Molecular Aspects Of The Stress Response Chaperones Membranes And Networks
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Author : Peter Csermely
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-08-09
Molecular Aspects Of The Stress Response Chaperones Membranes And Networks written by Peter Csermely and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-08-09 with Science categories.
This book makes a novel synthesis of the molecular aspects of the stress response and long term adaptation processes with the system biology approach of biological networks. Authored by an exciting mixture of top experts and young rising stars, it provides a comprehensive summary of the field and identifies future trends.
Index Medicus
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Author :
language : en
Publisher:
Release Date : 2004
Index Medicus written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Medicine categories.
Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
Heart Failure A Companion To Braunwald S Heart Disease E Book
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Author : Douglas L. Mann
language : en
Publisher: Elsevier Health Sciences
Release Date : 2010-11-11
Heart Failure A Companion To Braunwald S Heart Disease E Book written by Douglas L. Mann and has been published by Elsevier Health Sciences this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-11-11 with Medical categories.
Dr. Douglas L. Mann, one of the foremost experts in the field, presents the 2nd Edition of Heart Failure: A Companion to Braunwald’s Heart Disease. This completely reworked edition covers the scientific and clinical guidance you need to effectively manage your patients and captures the dramatic advances made in the field over the last five years. Now in full color, this edition features eleven new chapters, including advanced cardiac imaging techniques, use of biomarkers, cell-based therapies and tissue engineering, device therapies, and much more. Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability. Compatible with Kindle®, nook®, and other popular devices. Use this Braunwald’s companion as the definitive source to prepare for the ABIM’s new Heart Failure board exam. Access the fully searchable contents of the book online at Expert Consult. This edition includes 67 new authors, who are experts in the field of heart failure Stay on the cutting edge with new chapters on: The latest practice guidelines for medical and device therapy Hemodynamic assessment of heart failure Contemporary medical therapy for heart failure patients with reduced and preserved ejection fraction Biomarkers in heart failure Pulmonary hypertension Management of co-morbidities in heart failure Mechanical cardiac support devices Get up to speed with the latest clinical trials, as well as how they have influenced current practice guidelines Explore what’s changing in key areas such as basic mechanisms of heart failure, genetic screening, cell and gene therapies, pulmonary hypertension, heart failure prevention, co-morbid conditions, telemedicine/remote monitoring, and palliative care
Carbon Monoxide And Cardiovascular Functions
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Author : Rui Wang
language : en
Publisher: CRC Press
Release Date : 2001-10-30
Carbon Monoxide And Cardiovascular Functions written by Rui Wang and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001-10-30 with Medical categories.
Akin to nitric oxide, carbon monoxide (CO) was initially viewed as a pure toxic gas, yet it has been recently demonstrated to be an important endogenous molecule of gas that has profound physiological and pathophysiological effects on the cardiovascular system. In spite of the growing understanding achieved in this field, until now a comprehensive
Inflammatory Cardiomyopathy Dcmi Pathogenesis And Therapy
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Author : Heinz-Peter Schultheiss
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-01-30
Inflammatory Cardiomyopathy Dcmi Pathogenesis And Therapy written by Heinz-Peter Schultheiss and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-01-30 with Medical categories.
Cardiomyopathy is one of the most frequent causes of heart failure. It is often associated with inadequate heart pumping or other heart function abnormalities. There are many different causes of the disease, therefore many different kinds of cardiomyopathies exist. This volume, written by a leading expert, focuses on inflammatory CM, belonging to the Dilated Cardiomyopathies (DCMi). It covers epidemiology/prognosis, pathology, immunology, diagnosis and treatment strategies.
The Adrenergic System In Cardiovascular Physiology And Pathophysiology 2nd Edition
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Author : Giuseppe Rengo
language : en
Publisher: Frontiers Media SA
Release Date : 2016-12-18
The Adrenergic System In Cardiovascular Physiology And Pathophysiology 2nd Edition written by Giuseppe Rengo and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-12-18 with Cardiovascular system categories.
Cardiovascular diseases pose an enormous clinical challenge, remaining the most common cause of death in the world. ß-adrenoceptors play an important role on cardiac, vascular and/or endothelial function at a cellular level with relevant applications in several cardiovascular diseases, such as heart failure and hypertension. G protein– coupled receptors (GPCRs), including ß-adrenergic receptors, constitute the most ubiquitous superfamily of plasma membrane receptors and represent the single most important type of therapeutic drug target. Sympathetic nervous system hyperactivity, which characterizes several cardiovascular diseases, such as heart failure and hypertension, as well as physiological ageing, has been proved to exert in the long-term detrimental effects in a wide range of cardiovascular diseases. Acutely, sympathetic hyperactivity represents the response to an insult to the myocardium, aiming to compensate for decreased cardiac output. This process involves the activation of beta-adrenergic receptors by catecholamine with consequent heart rate and cardiac contractility increase. However, long-term exposure of the heart to elevated norepinephrine and epinephrine levels, originating from sympathetic nerve endings and chromaffin cells of the adrenal gland, results in further progressive deterioration in cardiac structure and function. At the molecular level, sustained sympathetic nervous system hyperactivity is responsible for several alterations including altered beta-adrenergic receptor signaling and function (down-regulation/ desensitization). Moreover, the detrimental effects of catecholamine affect also the function of different cell types including, but not limited to, endothelial cells, fibroblasts and smooth muscle cells. Thus, the success of beta-blocker therapy is due, at least in part, to the protection of the heart and the vasculature from the noxious effects of augmented catecholamine levels. The research topic aimed to support the progress towards understanding the role of sympathetic nervous system under physiological conditions, and the contribution of its hyperactivity in the pathogenesis and progression of cardiovascular diseases.