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Autophagy And Cardiometabolic Diseases

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Autophagy and Cardiometabolic Diseases

Autophagy and Cardiometabolic Diseases Book
Author : Jun Ren,James R. Sowers,Yingmei Zhang
Publisher : Academic Press
Release : 2018-04-12
ISBN : 0128054425
Language : En, Es, Fr & De

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Book Description :

Autophagy and Cardiometabolic Diseases: From Moleculer Mechanisms to Translational Medicine covers the science of autophagy in relation to cardiometabolic diseases and the future therapeutic potentials of autophagy regulation in these processes. Processes are not described in isolation, but in concert with other cellular and/or metabolic processes, such as lipogenesis, glucose, energy metabolism and apoptosis. This approach recognizes the multifactorial nature of cardiometabolic diseases, including obesity, diabetes, insulin resistance, hypertension and dyslipidemia. The book provides explanations, while also distinguishing the delicate role for autophagy in pathogenesis and exploring complications for cardiometabolic diseases. By targeting autophagy, it offers new avenues for drug discovery and treatment for cardiometabolic anomalies. It is a perfect resource for cardiology researchers, scientists and medical practitioners. Explains the processes inherent in the protein quality control for pathogenesis and complications of cardiometabolic diseases Provides knowledge from internationally recognized contributors in the field Incorporates a translational approach, covering the basic cellular biology of autophagy and presenting the role of autophagy regulation for both pathogenesis and complication in cardiometabolic diseases Contains access to a companion website with additional illustrations

Autophagy and Protein Quality Control in Cardiometabolic Diseases

Autophagy and Protein Quality Control in Cardiometabolic Diseases Book
Author : Jun Ren
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Autophagy and Protein Quality Control in Cardiometabolic Diseases book written by Jun Ren, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

New Drug Targets for Proteotoxicity in Cardiometabolic Diseases

New Drug Targets for Proteotoxicity in Cardiometabolic Diseases Book
Author : Jun Ren,Xin Wang,Ying Mei Zhang
Publisher : Frontiers Media SA
Release : 2021-11-02
ISBN : 2889715833
Language : En, Es, Fr & De

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Book Description :

Download New Drug Targets for Proteotoxicity in Cardiometabolic Diseases book written by Jun Ren,Xin Wang,Ying Mei Zhang, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

The Autophagy lysosome System in Cardiometabolic Disease

The Autophagy lysosome System in Cardiometabolic Disease Book
Author : Trent D. Evans
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The accumulation of dysfunctional proteins and organelles is a defining feature of metabolic disease in nearly every tissue. A key pathway addressing this challenge is the autophagy-lysosome system which serves to identify, sequester, and degrade cellular components. Here, I first report on harnessing TFEB, a transcription factor master regulator of genes involved in autophagy-lysosome biogenesis, lipid metabolism, and mitochondrial metabolism to drive this pathway in adipocytes. We found that TFEB overexpression protects mice from diet induced obesity and adverse metabolic sequelae including insulin resistance and hepatic steatosis. TFEB modestly induces expression of autophagy and lysosomal genes, but this targeting seemed insufficient to explain the observed metabolic phenotypes. Instead, we found that TFEB robustly induced expression of mitochondrial and lipid metabolic genes, resulting in enhanced thermogenesis. We identified the transcriptional coactivator PGC-1[alpha] as a key target of TFEB in adipocytes and demonstrated that TFEB-induced effects were largely PGC-1[alpha] dependent. These studies position TFEB as a potent regulator of adipocyte physiology with implications for targeting this pathway therapeutically.Second, I functionally characterized genetic variants in the Lysosomal Acid Lipase (LIPA) genetic risk locus for coronary artery disease. LIPA is the sole lysosomal cholesterol esterase crucial for lipid metabolism in the atherosclerotic plaque, and rare loss-of-function variants lead to severe cholesterol accumulation and early death. As a whole, we found the risk variants were associated with a gain-of-function in human monocyte enzyme activity and expression attributable to intronic variants in the locus. We also identified a single exonic variant in the risk locus resulting in the amino acid substitution T16P which could plausibly disrupt enzyme trafficking amounting to a net loss of function. Studied in isolation, however, the exonic variant did not functionally impair enzyme expression, secretion, stability, or trafficking to the lysosome. These results establish the LIPA risk locus for coronary artery disease as resulting from a gain-of-function and set the stage for future studies mechanistically exploring mechanisms of pathogenesis.

Intermittent Fasting to Unlock Hidden Potentials

Intermittent Fasting to Unlock Hidden Potentials Book
Author : Dr Leonard Cain
Publisher : Independently Published
Release : 2019-12-03
ISBN : 9781671220294
Language : En, Es, Fr & De

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Book Description :

Have you been trying to slim down unsuccessfully? Have you starved for days and weeks, only to regain all of the weight with crash dieting? If this is true, "Intermittent Fasting to Unlock Hidden Potentials" is the right book for you! In this book, you will learn: What is intermittent fasting; How to use it to your advantage; Why you're failing to lose weight despite doing the best you can to eat healthily; What are the true healing capacities of your own body, and how to eat to unlock the body's hidden potentials; How to trigger fast and permanent weight loss; How conventional dieting causes insulin resistance, and what you can do to start burning fat instead of your muscles to lose weight; How to fast easily and effectively while being full and satisfied; How to lose weight without calorie restriction; How to eat trigger Autophagy, the powerful process of self-healing, and How to recover from cardiometabolic diseases using the right foods; " Intermittent Fasting to Unlock Hidden Potentials" uses a scientific approach to present you with explanations for the most common causes of weight gain and health problems related to diet, such as: Obesity as a result of insulin resistance; Cardiometabolic disorders as a result of a maladjusted, habitual diet; Insulin resistance and its effects on metabolism and weight gain. Furthermore, "Intermittent Fasting to Unlock Hidden Potentials" will give you a thorough explanation of fasting, its origins and history, and the physiological reactions that happen as a result of it. In this book, you will learn about numerous scientifically verified benefits of fasting. You will learn how intermittent fasting can help you: Lose weight permanently with a simple, sustainable, and satisfying diet plan; Cure insulin resistance and turn your body into a fat-burning machine; Schedule your meals and exercises to grow muscle mass and burn the fatty tissue; Change your diet to support cardiovascular health and improve well-being; Identify how your diet affects your health and find the right strategies to support your health with natural foods; Learn how to use diet to strengthen your immune system, brainpower, and muscle power; and How to enhance the benefits of fasting by going on the Keto diet. Don't miss out on the opportunity to start burning fat in a matter of days and learn how to trigger some of the most powerful physiological processes of self-healing. Hurry and grab your copy of "Intermittent Fasting to Unlock Hidden Potentials" right now

Intermittent Fasting And Weight Loss

Intermittent Fasting And Weight Loss Book
Author : Omar Mascarena
Publisher : Unknown
Release : 2021-05-17
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Harness the health benefits of intermittent fasting--a comprehensive guide with meal plans and more Intermittent fasting (IF) is an evidence-based eating program that's existed in multiple forms for nearly 2,500 years, with roots in evolution and religion. That said, there are many ways to approach it and apply it to your life. This book is filled with essential information, how-to advice, FAQs, meal plans, and recipes to help you adopt and maintain an intermittent fasting lifestyle for weight loss and improved health. In this book, you will discover: - What is intermittent fasting; - How to use it to your advantage; - Why you're failing to lose weight despite doing the best you can to eat healthily; - What are the true healing capacities of your own body, and how to eat to unlock the body's hidden potentials; - How to trigger fast and permanent weight loss; - How conventional dieting causes insulin resistance, and what you can do to start burning fat instead of your muscles to lose weight; - How to fast easily and effectively while being full and satisfied; - How to lose weight without calorie restriction; - How to eat trigger Autophagy, the powerful process of self-healing, and - How to recover from cardiometabolic diseases using the right foods; - And so much more! Here's everything you need to apply intermittent fasting to your life so you can look and feel your best. Let's get started!

Exercise Autophagy and Chronic Diseases

Exercise  Autophagy and Chronic Diseases Book
Author : Ning Chen
Publisher : Springer Nature
Release : 2021-12-08
ISBN : 9811645256
Language : En, Es, Fr & De

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Book Description :

Download Exercise Autophagy and Chronic Diseases book written by Ning Chen, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Novel Concepts in Cardiac Energy Metabolism From Biology to Disease

Novel Concepts in Cardiac Energy Metabolism  From Biology to Disease Book
Author : Thomas Pulinilkunnil,Petra Kienesberger,Jeevan Nagendran
Publisher : Frontiers Media SA
Release : 2019-08-08
ISBN : 2889459381
Language : En, Es, Fr & De

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Book Description :

Download Novel Concepts in Cardiac Energy Metabolism From Biology to Disease book written by Thomas Pulinilkunnil,Petra Kienesberger,Jeevan Nagendran, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Characterization of Cardiac Autophagy in the Setting of Metabolic Syndrome Using Animal Models

Characterization of Cardiac Autophagy in the Setting of Metabolic Syndrome Using Animal Models Book
Author : Anonim
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Approximately 17 million people die of CVD. Obesity is considered to be a major risk factor which predisposes an individual to an increased risk of cardiovascular disease mortality. A clustering of risk factors such as obesity, insulin resistance and dyslipidemia results in the metabolic syndrome (MetS) which has a high prevalence rate of 23.7 percent of the US population. Several studies have shown that cellular autophagy is altered in the setting of metabolic syndrome and may contribute to cardiac dysfunction. However, the status of cardiac autophagic flux and autophagy-regulating pathways in the setting of MetS is unknown. The current literature implicates AMPK and mTOR, the key cellular energy sensors in the homeostatic regulation of autophagy. To test the hypothesis that cardiac autophagy is impaired in the setting of MetS mediated by changes in the upstream regulators- AMPK and mTOR, I used the diet-induced obese (DIO) mice and Zucker obese (ZO) rats (genetic model of obesity) as models of MetS. Under baseline conditions, the DIO mice showed impaired cardiac autophagic flux, a hyper-activated state of mTOR and a repressed state of AMPK. Under a physiological stress such as a fast, DIO mice showed impaired activation of cardiac autophagy despite intact responsiveness of the upstream regulators and intact gene expression. To examine the responsiveness of autophagy and that of its upstream regulators in cardiomyocytes sequestered from the extracellular milieu, I used adult rat ventricular cardiomyocytes (ARVM) isolated from ZO rats subjected to autophagy-inducing interventions. The ARVM from ZO rat hearts showed an impaired activation of autophagy despite intact responsiveness of the upstream regulators, similar to the profile observed in vivo. Overall, my results show that cardiac autophagy is indeed impaired in the setting of MetS despite the responsiveness of its regulatory pathways, AMPK and mTOR.

Cardiorespiratory Fitness in Cardiometabolic Diseases

Cardiorespiratory Fitness in Cardiometabolic Diseases Book
Author : Peter Kokkinos,Puneet Narayan
Publisher : Springer
Release : 2019-03-18
ISBN : 3030048160
Language : En, Es, Fr & De

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Book Description :

This book examines the links between physical activity (PA), cardiorespiratory fitness (CRF), and cardiovascular and metabolic diseases. It presents an overview of the role of PA and CRF in the prevention and management of risk factors associated with cardiometabolic diseases such as hypertension, peripheral vascular disease, stroke, type 2 diabetes, metabolic syndrome, dyslipidemia, obesity, and atherosclerosis. In addition, it explores how these risks vary with different populations such as the elderly and people of various racial backgrounds. The book also highlights risks associated with exercise and presents a prescription for appropriate and efficacious exercise to minimize risk and maximize health benefits for the heart. Cardiorespiratory Fitness in Prevention and Management of Cardiometabolic Disease is an essential resource for physicians, exercise physiologists, medical students, residents, fellows, nurses, and researchers in cardiology, cardiorespiratory fitness, exercise science, health promotion and disease prevention, public health, and epidemiology.

Mitochondrial Dysfunction and Cardiovascular Diseases

Mitochondrial Dysfunction and Cardiovascular Diseases Book
Author : Sebastiano Sciarretta,Richard N. Kitsis,Junichi Sadoshima
Publisher : Frontiers Media SA
Release : 2021-03-04
ISBN : 2889665569
Language : En, Es, Fr & De

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Book Description :

Download Mitochondrial Dysfunction and Cardiovascular Diseases book written by Sebastiano Sciarretta,Richard N. Kitsis,Junichi Sadoshima, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Role of Environmental and Genetic Effect in Cardiomyopathy

Role of Environmental and Genetic Effect in Cardiomyopathy Book
Author : Qiurong Wang
Publisher : Unknown
Release : 2016
ISBN : 9781339767383
Language : En, Es, Fr & De

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Book Description :

Cardiovascular disease is the leading cause of death in the US and other parts of the world. Various concurrent risk factors are associated with the ever-rising prevalence of heart diseases. Cardiovascular diseases are resulted from a complex interaction between environmental and genetic factors. Although environmental factors play an important role in heart disease, genetic factors are key determinants as well. In this dissertation research, I examined compromised cardiac geometric and contractile function in particular in the form of cardiomyopathies caused by environmental toxic stress, genetic mutation-induced insulin resistance and maternal obesity. Environmental risk factors are known to contribute to heart diseases. Among the environmental toxins, paraquat, a widely used non-selective herbicide, induces cardiotoxicity leading to myocardial injury and contractile dysfunction. Ablation of the essential post-receptor insulin signaling molecule Akt2 ablation conferred insulin resistance which is associated with high incidence of heart disease. Finally, maternal overnutrition and maternal obesity have been shown to contribute to the obesity pandemics in the 21st century and represent a good example for the interaction between environment and genetics, which negatively impact fetal heart development and cardiac health later on in life. Autophagy is a highly regulated intracellular lysosomal-mediated catabolic process which degrades aged, damaged or dysfunctional proteins, intracellular organelles and cytoplasmic components for maintaining cellular homeostasis. Autophagy is a double-edged sword, in some cases it acts as an adaptive response to stress for organismal survival, whereas in other cases it may promote cell death. Autophagy plays an essential role in cardiac homeostasis. Under normal conditions, basal level of autophagy is crucial for organelle turnover. Autophagy levels may be either up- or down-regulated in response to stresses such as ischemia/reperfusion, environmental toxins, insulin resistance and high caloric intake, contributing to cardiac remodeling and heart failure. Thus, the overall aim for my PhD research was to use autophagy as a cellular survival/death regulatory mechanism to examine the role of environmental and genetic factors in myocardial dysfunction and ultimately heart disease under various pathological conditions including paraquat toxicity and Akt2 deletion-induced insulin resistance. In order to examine the influence of maternal obesity on fetal sheep cardiomyocyte contractile and intracellular Ca2+ transient function, I established a novel method of assessment on fetal sheep cardiomyocyte function. First, my data indicated that paraquat-induced cardiac dysfunction was associated with excessive autophagy, which was ameliorated by AMPK deficiency. Furthermore, my data revealed that downregulation of autophagy from AMPK deficiency was mediated through AMPK-TSC2-mTORC1-ULK1 pathway. Secondly, I evaluated the effect of Akt2 ablation induced insulin resistance on diabetic cardiomyopathy, with a focus on the role of apoptosis and autophagy. I found that Akt2 knockout-induced insulin resistance caused cardiac anomalies was mediated via suppressed autophagy and activated apoptosis by decreased FOXO1 and increased p38 MAPK activity, which was effectively attenuated by the mTOR-independent inducer of autophagy trehalose. More intriguingly, activation of FOXO1 which facilitates the expression of autophagy related genes; and inhibition of p38 MAPK which suppresses the activity of Atg9, seem to be involved in trehalose-induced autophagy, in an mTOR-independent fashion. Finally, I successfully established a novel method for measuring mechanical and intracellular Ca2+ properties in fetal sheep cardiomyocytes. My data indicated that maternal obesity caused fetal sheep cardiomyocyte contractile dysfunction and disrupted intracellular Ca2+ homeostasis. Taken together, these findings provide some evidence to suggest that environmental and genetic factors play an important role in heart disease.

Non coding RNAs at the Cross Road of Cardiometabolic Diseases and Cancer

Non coding RNAs at the Cross Road of Cardiometabolic Diseases and Cancer Book
Author : Paul Holvoet
Publisher : Springer Nature
Release : 2021
ISBN : 3030688445
Language : En, Es, Fr & De

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Book Description :

This book gives insight into the functional role of non-coding RNAs in central pathways contributing to the development of obesity, type 2 diabetes, non-alcoholic fatty liver disease, atherosclerosis, myocardial infarction, cardiomyopathy, and heart failure. It also sheds light on the relationship of this cluster with cancer. Tumor cells, in contrast to cells in cardiometabolic tissues, can regulate this cluster of non-coding RNAs to escape from oxidative stress and anti-tumor immunity and maintain insulin sensitivity, facilitating cancer progression. The book presents a cluster of non-coding RNAs that may be prospectively analyzed in extensive cohort studies to determine their value in risk-predicting machine learning algorithms. In addition, it emphasizes the role of microvesicles in communication between tumor-adjacent tissue, inflammatory cells, and tumor cells, with a special focus on the role of miR-155. The book intends to promote interdisciplinary research. Due to the comprehensive background information provided in each chapter, it is suitable for researchers in academia and industry and for graduate students in biology, bioengineering, and medicine. .

Medicinal Plants for Cardiovascular and Neurodegenerative Aging related Diseases From Bench to Bedside

Medicinal Plants for Cardiovascular and Neurodegenerative Aging related Diseases  From Bench to Bedside Book
Author : Yue Liu,Valentina Echeverria Moran,Youhua Xu
Publisher : Frontiers Media SA
Release : 2020-12-08
ISBN : 2889661601
Language : En, Es, Fr & De

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Book Description :

Download Medicinal Plants for Cardiovascular and Neurodegenerative Aging related Diseases From Bench to Bedside book written by Yue Liu,Valentina Echeverria Moran,Youhua Xu, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Autophagy

Autophagy Book
Author : Xihui Xu,Jun Ren
Publisher : Elsevier Inc. Chapters
Release : 2013-09-03
ISBN : 012806949X
Language : En, Es, Fr & De

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Book Description :

Obesity, defined as accumulation of excessive body fat, has grown dramatically and imposes a devastating, pandemic health threat. If uncorrected, obesity may confer an increased susceptibility to the onset and development of insulin resistance, hypertension, type 2 diabetes, and the cadre of metabolic syndrome. More importantly, evidence from our group and other laboratories has demonstrated that obesity contributes to the development of cardiac anomalies. Although multiple signaling pathways have been identified as responsible for cardiac dysfunction in obese individuals, the precise mechanism still remains elusive. The autophagy–lysosome pathway, which regulates the degradation of large intracellular organelles and protein aggregates, is essential for the maintenance of cardiomyocytes under physiological and pathological conditions. Recent studies have suggested that the autophagy pathway plays a pivotal role in the development of cardiac anomalies induced by obesity. In the present chapter, we focus on how autophagy is involved in the regulation of cardiac function in obesity and metabolic syndrome.

Charnolophagy in Health and Disease

Charnolophagy in Health and Disease Book
Author : Sushil Sharma
Publisher : CRC Press
Release : 2021-09-03
ISBN : 1000298418
Language : En, Es, Fr & De

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Book Description :

This book introduces charnolophagy (CP) as energy-driven, lysosomal-dependent mitochondrial inclusion-specific pleomorphic Charnoly body (CB) autophagy (ATG) involving free radical-induced Ca2+ dyshomeostasis, ΔΨ collapse, and ATP depletion in congenital diseases, pressure ulcers, metabolic diseases, hepatic diseases, diabetes, obesity, inflammatory diseases, musculoskeletal diseases, sarcopenia, cachexia, respiratory diseases, gastrointestinal diseases, hyperlipidemia, skin and hair diseases, pulmonary diseases, cardiovascular diseases, renal diseases, sepsis-induced multi-organ failure, reproductive diseases, inflammatory diseases, ophthalmic diseases, neurodegenerative diseases, drug addiction, aging, microbial (including COVID-19) infections, and belligerent malignancies implicated in early morbidity and mortality and disease-specific spatiotemporal, targeted, safe, and effective evidence-based personalized theranostic charnolopharmacotherapeutics to cure them. Basic DRESS and GELS principles, nanoparticles to cure chronic multidrug-resistant (MDR) diseases, antioxidants as free radical scavengers, CB antagonists, CP regulators, and CS stabilizers to curb CB molecular pathogenesis (CBMP) are described for better quality of life and longevity. Specific guidelines for environmental protection and preservation of zoological and botanical species at the verge of extinction, Triple "I" Hypothesis for mitochondrial quality control, and transcriptional regulation of CSexR and CSendoR to cure chronic diseases are presented. Novel CP index is introduced to evaluate MDR malignancies and other chronic diseases. WHO, CDC, FDA, NIH, policy planners, cosmetologists, trichologists, players, athletes, dancers, wrestlers, equestrians, young women, aging population, toxicologists, environmental protectionists, pharmaceutical industry, biomedical scientists, researchers, medical students, physicians, nurses, paramedical professionals, and global audience will be interested in this interesting book to prevent pandemics and raise healthcare awareness.

Mitochondrial Remodeling and Dynamic Inter Organellar Contacts in Cardiovascular Physiopathology

Mitochondrial Remodeling and Dynamic Inter Organellar Contacts in Cardiovascular Physiopathology Book
Author : Giampaolo Morciano,Gaetano Santulli,Valentina María Parra,Giovanni Monaco
Publisher : Frontiers Media SA
Release : 2021-06-21
ISBN : 2889669424
Language : En, Es, Fr & De

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Book Description :

Download Mitochondrial Remodeling and Dynamic Inter Organellar Contacts in Cardiovascular Physiopathology book written by Giampaolo Morciano,Gaetano Santulli,Valentina María Parra,Giovanni Monaco, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Autophagy in Health and Disease

Autophagy in Health and Disease Book
Author : Roberta A. Gottlieb
Publisher : Academic Press
Release : 2012-10-16
ISBN : 0123851017
Language : En, Es, Fr & De

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Book Description :

Autophagy in Health and Disease offers an overview of the latest research in autophagy with a translational emphasis. This publication takes scientific research in autophagy a step further and offers integrated content with advancements in autophagy from cell biology and biochemical research to clinical treatments. A necessary reference for the bookshelf of medical and scientific researchers and students, Autophagy in Health and Disease presents high quality, reputable information on autophagy, allowing the reader quick access to the most applicable information. Discusses current understanding of the roles of autophagy in health and disease Covers the background of autophagy, the development of tools and therapeutics to measure and modulate autophagy, and autophagy in tissues and disease processes Features an accompanying website with figures and tables

The Role of Autophagy in Cardiac Aging and Aging associated Chronic Diseases

The Role of Autophagy in Cardiac Aging and Aging associated Chronic Diseases Book
Author : Shuyi Wang
Publisher : Unknown
Release : 2019
ISBN : 9781658420815
Language : En, Es, Fr & De

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Book Description :

Aging is becoming an escalating issue in the world as human life expectancy continues to rise. Advanced aging imposes a cadre of chronic disease including cardiovascular diseases. The aging heart displays unfavorable changes in both geometry and function including increased left ventricular (LV) mass, reduced cardiac reserve capacity, myocardial fibrosis and increased risk of arrhythmia, contributing to poor exercise capacitance (effort intolerance) and frailty in the elderly. In addition, aging also increases the risk of many chronic diseases that jeopardize the cardiovascular function and quality of life in the elderly. With progressive aging, several pathological conditions including obesity, type II diabetes mellitus, Alzheimer’s disease and cancer are on the horizon. For example, obesity has been considered as a trigger for premature aging, leading to pathological cardiac remodeling and compromised ventricular function. Alzheimer’s disease is a neurodegenerative disease featured by accumulation of amyloid plaque and neurofibrillary tangles. Alzheimer’s disease may provoke cardiovascular dysfunction impairment of diastolic function. Over the past decades intense effort has been made towards understanding the mechanistic framework behind aging, obesity and Alzheimer’s disease in the pathogenesis of cardiovascular anomalies. An emerging role of dysregulated autophagy, a conservative homeostatic process for cellular quality control by way of disposal and recycling of cellular components, has surfaced in cardiac anomalies under all these pathological settings. To this end, this dissertation research will focus on the underlying mechanism of cardiac remodeling and contractile dysfunction during the normal aging process, as well as aging-associated conditions such as obesity and Alzheimer’s disease. The major findings from my work revealed that (1): Ablation of TLR4 restores autophagy level through the regulation of NCoR1/HDAC and improves heart function in aging; (2): Knocking out of Akt and AMPK facilitates premature cardiac aging in a joint manner; (3): Mitochondrial aldehyde dehydrogenase (ALDH2) overexpression protects obese heart through SUV39H1-Sirt1 signaling; and (4): Melatonin protects Alzheimer’s disease-associated heart dysfunction through cGAS-STING regulated autophagy in the presence of ALDH2.

Role of Autophagy in Cardiac Stress

Role of Autophagy in Cardiac Stress Book
Author : Xihui Xu,University of Wyoming. Biomedical Sciences Graduate PhD Program
Publisher : Unknown
Release : 2013
ISBN : 9781303150746
Language : En, Es, Fr & De

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Book Description :

Various stimuli, including a high dietary fat, starvation, pressure overload and administration of certain drugs, have been shown to cause cardiac stress and compromise myocardial function. Among the various factors, chronic intake of HFD has been deemed to be the major contributor to the development of obesity. If uncorrected, obesity promotes the onset and development of cardiac hypertrophy and myocardial dysfunction, contributing to the high cardiac morbidity and mortality in obese individuals. In contrast to nutrition overload, malnutrition or starvation has been shown to cause cardiac geometry and function changes. In addition to the nutrition disturbance, increased pressure overload is another major factor for the development of cardiac hypertrophy and myocardial dysfunction. Initially, it is an adaptive and beneficial process; however, sustained pressure overload triggers its transition to be maladaptive and finally develops to the stage of heart failure. The development of cardiomyopathy, and even heart failure, can also be attributed to the side effects of certain drugs, that are used for the treatment of other diseases. Among these drugs, anticancer agent doxorubicin is extensively studied because of its protective effect against cancer and its high cardiotoxicity. As one of the most powerful anticancer drugs, doxorubicin has been used for more than 80 years. However, accumulating studies have demonstrated the fatal cardiotoxic side effects of doxorubicin treatment. Autophagy is an evolutionarily conserved cellular pathway involved in degradation and recycling of long-lived intracellular proteins and cytoplasmic organelles. In theory, autophagy can either promote cell survival or cell death. On one hand, autophagy is protective through clearing off the damaged organelles and dysfunctional proteins, or through refreshing the amino acid pool and providing new intracellular energy. However, on the other hand, over-activated autophagy could be detrimental through the excessive degradation of essential cellular constituents. Under physiological conditions, the basal level of autophagy plays an indispensable role in maintaining cardiac geometry and function through degrading intracellular components and supplying intracellular energy. Although autophagy activity is maintained at low-levels in the heart under physiological conditions, it is susceptible for disturbance by a number of cardiovascular diseases including ischemia-reperfusion, pathological hypertrophy, and heart failure. However, the role of autophagy in the heart under different pathological conditions is still controversial. Thus the objective of my PhD project was to study whether, and how, cardiac autophagy is involved in maintaining cardiac function under different pathological conditions including HFD-induced obesity and type II diabetes, starvation-induced cardiac injury, pressure overload-induced cardiac hypertrophy and doxorubicin-induced cardiomyopathy. Alterations in signaling key molecules involved in autophagy under HFD, starvation, pressure overload and doxorubicin challenge were explored. First, my data indicated that HFD-induced cardiac dysfunction was associated with disruption of the autophagosome maturation process, which could be rescued by Akt2 knockout. Furthermore, my data demonstrated that rescuing defective autophagosome maturation processes is pivotal for the cardioprotective effect of Akt2 knockout against high fat diet-induced obesity. Secondly, we evaluated the role of MIF (macrophage migration inhibitory factor) in HFD-induced obesity and diabetic cardiomyopathy, with a focus on the role of inflammation and autophagy. We observed that MIF deficiency did not prevent HFD-induced obesity and whole-animal energy utilization disturbance. Interestingly, our results showed that MIF deficiency prevented HFD-induced diabetic cardiomyopathy. The cardioprotective effect of MIF deficiency is associated with improved myocardial inflammation and autophagy in HFD-induced diabetic myocardium. Thirdly, we studied if and how MIF is involved in cardiac geometry and function changes during starvation. Our results showed that MIF knockout was able to unmask starvation-induced cardiac injury. Although the underlying mechanisms are complex, our data suggests that MIF plays a permissive role in the maintenance of cardiac geometry and function under starvation by regulation of autophagy. Fourthly, my study showed autophagy activation was beneficial in protecting cardiac hypertrophy exacerbation under pressure overload. More importantly, pressure overload-induced cardiac autophagy activation was shown to be mediated by MIF through activating AMPK and inhibiting mTOR activity. Besides, mitochondrial autophagy (mitophagy) was found to be a dominant form of MIF-mediated autophagy in pressure overload-induced hypertrophic heart. The cardiac toxicity of doxorubicin was shown to be associated with disrupted cardiac autophagic flux activity, the effect of which is exacerbated by MIF knockout. Rescuing autophagy by rapamycin treatment dramatically attenuated doxorubicin-induced cardiac dysfunction and mortality in MIF−[superscript]/ − mice. Taken together, these data provide evidence suggesting that autophagy is beneficial in maintaining cardiac function under pathological stress conditions including HFD-induced obesity and type II diabetes, pressure overload-induced cardiac hypertrophy and doxorubicin-induced heart failure.