Hypoxia Signaling in Cardiovascular Diseases

Cardiovascular diseases such as stroke, coronary artery disease, and thrombosis remain a global health burden. Understanding the mechanism of these diseases paves the way for development of prophylactics/therapeutics. It is well known at cellular levels; the pathophysiology of most of the cardiovascular disease involves a complicated yet coordinated signaling networks triggered in response to either cellular or tissue levels of hypoxic milieu. Information related to types of hypoxia and signaling mechanism associated to such complications if complied and presented in a comprehensive manner shall prove relevant in proposing common therapeutic targets for wide array of cardiovascular complications. The relative functional roles of hypoxia-triggered signaling pathways are also an area of current research. Based upon these facts, this chapter discusses the types of hypoxia and role of hypoxia-mediated signaling pathways in various types of commonly occurring cardiovascular disorders

Application of Metabolomics for the Diagnosis and Traditional Chinese Medicine Syndrome Differentiation of Chronic Heart Failure

Chronic heart failure (CHF) was characterized by the failure of enough blood supply from the heart to meet the body’s metabolic demands, and the prevalence of CHF continuously increases globally. The personalized diagnosis of Traditional Chinese Medicine (TCM) classifies CHF into several different syndrome types, and integrating Western and TCM to treat CHF has proved a validated therapeutic approach. Over the last few years, there has been a rapidly growing number of metabolomics applications aimed at finding biomarkers that could assist diagnosis, provide therapy guidance, and evaluate response to therapy for individualized intervention of CHF. Thus, in this review, particular attention will be paid to the past successes in applications of state-of-the-art technology on metabolomics to contribute to biomarker discovery in CHF research

Relação entre estresse, depressão, alterações cardiometabólicas e exercício físico

Stress is considered one of the most significant health problems in modern society. It can be characterized as any changes in the homeostasis of an individual that require an adaptive response. An imbalance in the secretion of the primary stress mediators may be responsible for the onset and development of several diseases. Thus, chronic stress has been recognized as a risk factor for depression as well as cardiovascular and metabolic diseases. Given the pathophysiological mechanisms associated with chronic stress and related cardiovascular and metabolic changes, it is necessary to implement measures to prevent, control and/or avoid their development. Physical exercise is a non-pharmacological resource that is widely used for this purpose. Its beneficial effects include the improvement of the emotional state as well as lipid and glycemic control. Objective: The aim of this review is to discuss the relationship between stress, depression, cardiovascular and metabolic changes, and highlight the importance of physical exercise in the prevention and treatment of resulting disorders. Materials and Methods: We searched MEDLINE and SCIELO from 2000 through 2012, using the terms chronic stress, mood disorders, depression, cardiovascular and metabolic changes, and exercise. Results: Most of the studies found in our literature search have shown that exercise can attenuate and/or reverse the deleterious effects of chronic stress. Conclusion: Regular physical exercise is useful for maintaining health, especially with respect to improving mood and mental stress2912336CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP459056/2014-0;140926/2012-7Sem informação2010/51904-9O estresse é um dos mais significativos problemas de saúde na sociedade moderna, podendo ser caracterizado como qualquer mudança na homeostase do indivíduo que requer uma resposta adaptativa. O desequilíbrio na produção dos mediadores primários do estresse pode ser responsável pelo surgimento e desenvolvimento de várias doenças. Dessa forma, o estresse crônico tem sido reconhecido como fator de risco para a depressão e doenças cardiometabólicas. Frente aos mecanismos fisiopatológicos associados ao estresse crônico e às alterações cardiometabólicas correlatas, torna-se necessário encontrar medidas adequadas para preveni-las, controlá-las e/ou evitá-las. Sabe-se que o exercício físico é um recurso não-farmacológico amplamente utilizado para essa finalidade e os efeitos benéficos desencadeados incluem melhora do estado emocional e controle lipídico e glicêmico. Objetivo: O objetivo desta revisão foi discutir a relação entre os mecanismos fisiopatológicos do estresse, depressão, alterações cardiometabólicas e a importância da utilização do exercício físico na prevenção e tratamento destas disfunções desencadeadas. Materiais e Métodos: Para esta revisão foram consultadas as bases de dados MEDLINE e SCIELO e inclusos no campo de pesquisa os termos estresse crônico, alterações de humor, depressão, alterações cardíacas e metabólicas e o exercício físico. Como limite de busca, foi definida a pesquisa de artigos publicados entre os anos de 2000 e 2012. Resultados: A maior parte dos estudos mostrou que o exercício é capaz de atenuar e/ou reverter os efeitos deletérios do estresse crônico. Conclusão: A prática regular do exercício físico tem grande utilidade para a manutenção da saúde, sobretudo com relação à melhora do humor e do estresse menta

The Effects of LCN2 and Iron on Cardiac Remodeling and the Impact on Cardiac Function

Lipocalin-2 (Lcn2; also termed neutrophil gelatinase-associated lipocalin (NGAL)) is a proinflammatory factor which is elevated in obese individuals. It has also been implicated in the pathogenesis of heart failure and as a potential biomarker. This thesis exaimed: project 1: Regulation of autophagy by Lcn2 and its functional significance in leading to insulin resistance in cardiomyocytes, project 2: Changes in cardiac function, autophagy and cell death in wild type and Lcn2-knockout mice subjected to chronic myocardial ischemia, and project 3: Effect of iron on insulin sensitivity in cardiomyocytes and mechanistic role of oxidative stress. Findings from project 1 indicated that Lcn2 treatment caused insulin resistance and use of gain and loss of function approaches elucidated a causative link between autophagy inhibition and regulation of insulin sensitivity in response to Lcn2. Project 2 data demonstrated that Lcn2 attenuated autophagy to worsen the extent of apoptosis induced by chronic myocardial ischemia in mice. Finally, in project I showed that iron directly induced insulin resistance in cardiomyocytes and that this involved regulation of the crosstalk between autophagy and oxidative stress. In summary, my studies demonstrated that Lcn2 promoted cardiac dysfunction and that lack of Lcn2 in mice was protective against surgically-induced heart failure. Inhibition of autophagy played a central mechanistic role in mediating the detrimental effects of Lcn2 on the heart, which included elevated oxidative stress, cell death and insulin resistance

Atrial Myopathy

This paper discusses the evolving concept of atrial myopathy by presenting how it develops and how it affects the properties of the atria. It also reviews the complex relationships among atrial myopathy, atrial fibrillation (AF), and stroke. Finally, it discusses how to apply the concept of atrial myopathy in the clinical setting—to identify patients with atrial myopathy and to be more selective in anticoagulation in a subset of patients with AF. An apparent lack of a temporal relationship between episodes of paroxysmal AF and stroke in patients with cardiac implantable electronic devices has led investigators to search for additional factors that are responsible for AF-related strokes. Multiple animal models and human studies have revealed a close interplay of atrial myopathy, AF, and stroke via various mechanisms (e.g., aging, inflammation, oxidative stress, and stretch), which, in turn, lead to fibrosis, electrical and autonomic remodeling, and a pro-thrombotic state. The complex interplay among these mechanisms creates a vicious cycle of everworsening atrial myopathy and a higher risk of more sustained AF and strokes. By highlighting the importance of atrial myopathy and the risk of strokes independent of AF, this paper reviews the methods to identify patients with atrial myopathy and proposes a way to incorporate the concept of atrial myopathy to guide anticoagulation in patients with AF.S

Novel Strategies in Ischemic Heart Disease

The first edition of this book will provide a comprehensive overview of ischemic heart disease, including epidemiology, risk factors, pathogenesis, clinical presentation, diagnostic tests, differential diagnosis, treatment, complications and prognosis. Also discussed are current treatment options, protocols and diagnostic procedures, as well as the latest advances in the field. The book will serve as a cutting-edge point of reference for the basic or clinical researcher, and any clinician involved in the diagnosis and management of ischemic heart disease. This book is essentially designed to fill the vital gap existing between these practices, to provide a textbook that is substantial and readable, compact and reasonably comprehensive, and to provide an excellent blend of "basics to bedside and beyond" in the field of ischemic heart disease. The book also covers the future novel treatment strategies, focusing on the basic scientific and clinical aspects of the diagnosis and management of ischemic heart disease

Proteomic analysis of rat serum revealed the effects of chronic sleep deprivation on metabolic, cardiovascular and nervous system

Sleep is an essential and fundamental physiological process that plays crucial roles in the balance of psychological and physical health. Sleep disorder may lead to adverse health outcomes. The effects of sleep deprivation were extensively studied, but its mechanism is still not fully understood. The present study aimed to identify the alterations of serum proteins associated with chronic sleep deprivation, and to seek for potential biomarkers of sleep disorder mediated diseases. A label-free quantitative proteomics technology was used to survey the global changes of serum proteins between normal rats and chronic sleep deprivation rats. A total of 309 proteins were detected in the serum samples and among them, 117 proteins showed more than 1.8-folds abundance alterations between the two groups. Functional enrichment and network analyses of the differential proteins revealed a close relationship between chronic sleep deprivation and several biological processes including energy metabolism, cardiovascular function and nervous function. And four proteins including pyruvate kinase M1, clusterin, kininogen1 and profilin-1were identified as potential biomarkers for chronic sleep deprivation. The four candidates were validated via parallel reaction monitoring (PRM) based targeted proteomics. In addition, protein expression alteration of the four proteins was confirmed in myocardium and brain of rat model. In summary, the comprehensive proteomic study revealed the biological impacts of chronic sleep deprivation and discovered several potential biomarkers. This study provides further insight into the pathological and molecular mechanisms underlying sleep disorders at protein level

The Heart Is at Risk: Understanding Stroke-Heart-Brain Interactions with Focus on Neurogenic Stress Cardiomyopathy-A Review.

In recent years, it has been convincingly demonstrated that acute brain injury may cause severe cardiac complications-such as neurogenic stress cardiomyopathy (NSC), a specific form of takotsubo cardiomyopathy. The pathophysiology of these brain-heart interactions is complex and involves sympathetic hyperactivity, activation of the hypothalamic-pituitary-adrenal axis, as well as immune and inflammatory pathways. There have been great strides in our understanding of the axis from the brain to the heart in patients with isolated acute brain injury and more specifically in patients with stroke. On the other hand, in patients with NSC, research has mainly focused on hemodynamic dysfunction due to arrhythmias, regional wall motion abnormality, or left ventricular hypokinesia that leads to impaired cerebral perfusion pressure. Comparatively little is known about the underlying secondary and delayed cerebral complications. The aim of the present review is to describe the stroke-heart-brain axis and highlight the main pathophysiological mechanisms leading to secondary and delayed cerebral injury in patients with concurrent hemorrhagic or ischemic stroke and NSC as well as to identify further areas of research that could potentially improve outcomes in this specific patient population