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Author: Danielle R. Bruns Publisher: ISBN: Category : Medicine Languages : en Pages :
Book Description
Heart failure (HF) is a clinically complex and heterogenous disease characterized by an inability of the heart to pump sufficient blood to the periphery. As such, it has historically been thought of and studied as a disease of the left ventricle (LV). While LV failure is the most common form of HF, it is the ability of the right heart to function that predicts survival in many clinical settings. Extrapolation of mechanisms of left HF to the right ventricle (RV) has yet to prove fruitful in identification of therapeutic approaches, in large part due to a lack of basic mechanistic understanding of the RV which is embryologically, anatomically, and physiologically distinct from the LV. The failing LV is characterized by mitochondrial dysfunction and a metabolic switch, both of which contribute to an energetically starved heart with poor contractile ability. These mechanisms, however, are far less described in the failing RV. The purpose of this chapter is to present the current literature examining the role of mitochondria and metabolism in the healthy right heart, treatments to target deficits in the failing RV, and to identify knowledge gaps for future research in this clinically important area.
Author: Danielle R. Bruns Publisher: ISBN: Category : Medicine Languages : en Pages :
Book Description
Heart failure (HF) is a clinically complex and heterogenous disease characterized by an inability of the heart to pump sufficient blood to the periphery. As such, it has historically been thought of and studied as a disease of the left ventricle (LV). While LV failure is the most common form of HF, it is the ability of the right heart to function that predicts survival in many clinical settings. Extrapolation of mechanisms of left HF to the right ventricle (RV) has yet to prove fruitful in identification of therapeutic approaches, in large part due to a lack of basic mechanistic understanding of the RV which is embryologically, anatomically, and physiologically distinct from the LV. The failing LV is characterized by mitochondrial dysfunction and a metabolic switch, both of which contribute to an energetically starved heart with poor contractile ability. These mechanisms, however, are far less described in the failing RV. The purpose of this chapter is to present the current literature examining the role of mitochondria and metabolism in the healthy right heart, treatments to target deficits in the failing RV, and to identify knowledge gaps for future research in this clinically important area.
Author: Jose Guadalupe Gomez-Arroyo Publisher: ISBN: Category : Languages : en Pages : 388
Book Description
Right ventricular dysfunction is the most frequent cause of death in patients with pulmonary arterial hypertension. Although abnormal energy substrate use has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in failing right ventricular tissue remain incomplete. In the present dissertation we sought to characterize metabolic gene expression changes and mitochondrial dysfunction in functional and dysfunctional RV hypertrophy. Two different rat models of RV hypertrophy were studied. The model of right ventricular failure (SU5416/hypoxia) exhibited a significantly decreased gene expression of peroxisome proliferator-activated receptor- coactivator-1[alpha], peroxisome proliferator- activated receptor-[alpha] and estrogen-related receptor-[alpha]. The expression of multiple peroxisome proliferator-activated receptor- coactivator-1[alpha] target genes required for fatty acid oxidation was similarly decreased. Decreased peroxisome proliferator-activated receptor- coactivator-1[alpha] expression was also associated with a net loss of mitochondrial protein and oxidative capacity. Reduced mitochondrial number was associated with a downregulation of transcription factor A, mitochondrial, and other genes required for mitochondrial biogenesis. Electron microscopy demonstrated that, in right ventricular failure tissue, mitochondria had abnormal shape and size. Lastly, respirometric analysis demonstrated that mitochondria isolated from right ventricular failure tissue had a significantly reduced ADP- stimulated (state 3) rate for complex I. Conversely, functional right ventricular hypertrophy in the pulmonary artery banding model showed normal expression of peroxisome proliferator-activated receptor- coactivator-1[alpha], whereas the expression of fatty acid oxidation genes was either preserved or unregulated. Moreover, pulmonary artery banding-right ventricular tissue exhibited preserved transcription factor A mitochondrial expression and mitochondrial respiration despite elevated right ventricular pressure-overload. We conclude that right ventricular dysfunction, but not functional right ventricular hypertrophy in rats, demonstrates a gene expression profile compatible with a multilevel impairment of fatty acid metabolism and significant mitochondrial dysfunction, partially independent of chronic pressure-overload.
Author: Gaetano Santulli Publisher: Springer ISBN: 3319553305 Category : Science Languages : en Pages : 644
Book Description
This text covers the basic principles of mitochondrial dynamics in cardiovascular medicine, with particular emphasis on their functional roles in physiology and disease. The book will include articles pertaining to mitochondrial fitness on a global basis, providing therefore an update on the progress made in several aspects in the field. Thus, it will assist scientists and clinicians alike in furthering basic and translational research. Organized in sections focusing on: basic science, mitochondrial dysfunction in cardiac disorders, in vascular disorders, in metabolic disorders, in kidney disease, therapeutic challenges and options, this essential volume fills imperative gaps in understanding and potentially treating several cardiovascular disorders.
Author: H. Böhles Publisher: CRC Press ISBN: 9783887631048 Category : Cardiomyopathy Languages : en Pages : 188
Book Description
During the last years the understanding for the aetiology of cardiomyopathies could be greatly improved. A great deal of information has accumulated in the field of inherited metabolic diseases, which provides a new basis for our understanding of many heart muscle problems and their corresponding clinical disease entities. This book is meant to give the reader a comprehensive overview of the cardiological manifestations of inborn errors of metabolism. Latest information, such as cardiomyopathy in Fabry disease or in patients with CDG-syndrome is included. It should be helpful, not only to cardiologists, paediatricians, internists and general practicioners, but also to all those interested in a better understanding of the metabolic basis of clinical disease entities.
Author: José Marín-García Publisher: Springer Science & Business Media ISBN: 0387255745 Category : Medical Languages : en Pages : 415
Book Description
Mitochondria have been pivotal in the development of some of the most important ideas in modern biology. Since the discovery that the organelle has its own DNA and specific mutations were found in association with neuromuscular and cardiovascular diseases and with aging, an extraordi-nary number of publications have followed, and the term mitochondrial medicine was coined. Furthermore, our understanding of the multiple roles that mitochondria play in cardiac cell homeostasis opened the door for intensive experimentation to understand the pathogenesis and to find new treatments for cardiovascular diseases. Besides its role in adenosine triphosphate generation, mitochondria regu-late a complex network of cellular interactions, involving (1) generation and detoxification of reactive oxygen species, including superoxide anion, hy-drogen peroxide, and hydroxyl radical; (2) maintenance of the antioxidant glutathione in a reduced state and adequate level of mitochondrial matrix superoxide dismutase; (3) cytoplasmic calcium homeostasis, particularly under conditions of cellular calcium loading; (4) transport of metabolites between cytoplasm and matrix; (5) both programmed (apoptosis) and necrotic cell death; and (6) cell growth and development. It is therefore not surprising that this organelle has come to be the center stage in many current investigations of cardiovascular diseases, aging, and agi- related disease. Concomitant with these advances, an impressive effort is under- way for the development of new tools and methodologies to study mitochondrial structure and function, including powerful ways to visualize, monitor, and alter the organelle function to assess the genetic consequences of these perturbations.
Author: Lawrence H. Lash Publisher: Elsevier ISBN: 1483218619 Category : Science Languages : en Pages : 527
Book Description
Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
Author: Joanne S. Ingwall Publisher: Springer Science & Business Media ISBN: 1461510937 Category : Medical Languages : en Pages : 272
Book Description
ATP plays a central role in the two leading causes of cardiac morbidity and mortality in the western world: ischemia and heart failure. We are in our infancy applying what is known about biology and chemistry of ATP toward developing effective therapies for these diseases. In this volume, the current understanding of the chemistry and biology of ATP specifically in the cardiomyocyte is presented. New insights into ATP have been gleaned using biophysical techniques allowing dynamic measurement of chemical events in the intact beating heart and using new animal models in which cardiac proteins are either over expressed, deleted or harbor specific mutations. This book provides a summary of the basic understanding and includes illustrations of why ATP and the Heart is important to both the clinician and scientist.
Author: Arianne Caudal Publisher: ISBN: Category : Languages : en Pages : 172
Book Description
Cardiovascular disease is the leading cause of death worldwide, yet developments of new treatment has been stalled for nearly three decades and novel concepts and strategies are urgently needed. Mitochondria play a central role in cardiac physiology due to the extraordinary energy demands of the heart. It is well recognized that mitochondrial and metabolic remodeling can be maladaptive in the cardiac response to acute and chronic stress, therefore, treatments that specifically target mitochondrial metabolism would be highly desirable. Our limited understanding of mechanisms that connect mitochondrial dysfunction to cellular responses to stress has hindered progress of therapeutic innovation. In order to gain a more comprehensive understanding of the mitochondrial compartment, we used cross-linking mass spectrometry to determine the protein interaction landscape in respiring isolated mitochondria, intact cardiac tissue, and from animal models of heart failure. These efforts uncovered structural insight into how proteins behave in their native environments and in the presence of pathological stress. Comprehensive visualization of the diverse mitochondrial protein landscape is expected to pave for new therapies and novel drug candidates for heart failure. Furthermore, advancement of a technological strategy for system-wide study of proteins is applicable across a wide range of both physiological and pathological systems and models.
Author: Danielle R. Bruns
Author: Danielle R. Bruns
Author: Shijun Wang
Author: Jose Guadalupe Gomez-Arroyo
Author: Gaetano Santulli
Author: H. Böhles
Author: José Marín-García
Author: Sebastiano Sciarretta
Author: Lawrence H. Lash
Author: Joanne S. Ingwall
Author: Arianne Caudal