The Renin Angiotensin System in Cancer, Lung, Liver and Infectious Diseases

Description:

This book of the series on “Advances in Biochemistry in Health and Disease” includes state-of-the-art information on the status of renin-angiotensin system (RAS) in the form of 24 chapters. This book has been organized into three sections: (i) General Implications of RAS in human health and Infectious Diseases, (ii) Lung, Liver and Kidney Diseases, and (iii) Development of Cancer. Each chapter has discussed comprehensive knowledge regarding the molecular and cellular aspects of the role of RAS in the pathophysiology and pharmacotherapy of different disease processes. Biochemical mechanisms associated with angiotensin II type 1 and type II receptors, and angiotensin (1-7) MAS receptors for the occurrence of both harmful and beneficial effects of prolonged activation of RAS in different diseases have been outlined. It is noteworthy to point out that different chapter in this book were prepared by recognized global expertise in the area of inflammation, oxidative stress and signal transduction pathways to highlight the role of RAS in different diseases. It is our sincere hope that this book will be of great interest to both biomedical investigators and health professionals as well as graduate students and postdoctoral fellows all over the world.

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Preface

The renin-angiotensin system (RAS) has been an extensively studied system in human health and disease. The common precursor of all RAS hormones, angiotensinogen, which is primarily formed in the liver, is cleaved by enzyme renin (secreted from the kidneys) to produce angiotensin (Ang) I. This peptide is further cleaved to form Ang II by angiotensin-converting enzyme (ACE) in the lungs. Activation of different signal transduction pathways by Ang II is mediated by Ang-receptors (Ang II type 1 and Ang II type 2), resulting in proliferative or antiproliferative effects. Increased Ang II levels caused by chronic activation of RAS influence several processes including proliferation, apoptosis, autophagy, migration, cellular metabolism, Ca2+-handling, inflammation, oxidative stress and angiogenesis. Ang I is also converted to Ang (1-7) by ACE2, which activates mitochondrial assembly (MAS) receptors to produce anti-proliferative actions and other beneficial effects. Apart from the existence of RAS in the circulatory system, as well as locally in the heart, this system is also operational in the brain, pituitary gland, adrenal gland, prostate gland, endometrium, pancreas, mammary gland, ovaries, testis and epididymis. In addition to cardiovascular diseases (CVDs), the disruption in the expression or activity of RAS components also manifests in other multiple pathologies, including cancer, liver disease, lung abnormalities, infectious diseases and renal dysfunction. Furthermore, pharmacological or the therapeutic efficacy of the blockade of RAS by the Ang II receptor blockers and/or ACE inhibitors has been designed to normalize RAS over-activation for the treatment of these diseases.

The role of RAS in the pathogenesis of CVDs has been described in an earlier volume of this series. Since cancer and diseases of the liver, lung and kidney as well as infectious diseases are the leading cause of death worldwide after CVDs, exploration of underlying physiological, pathological, and pharmacological aspects of these diseases and the contribution of RAS to these processes have remained a global focus of investigation in health and disease. Indeed, there has been a remarkable expansion of studies on the implication of RAS over-activation in these diseases. Accordingly, this book is intended to summarize the role of RAS in the pathogenesis of these diseases as well as the potential of RAS blockade as a novel therapeutic approach. In this regard, basic concepts of RAS and the role of RAS in the pathogenesis of infectious diseases such as COVID-19, viral hepatitis, pneumonia and influenza are also described. In addition, the role of RAS in the processes involved in carcinogenesis, such as proliferative signal transduction, microenvironment interactions, cellular and molecular dysregulation and metabolic disturbances, is discussed. Also included in this book are chapters that address pre-clinical and clinical studies which identify modulation of RAS as an effective treatment for cancer.

It is now well known that RAS elicits the pathophysiology of different liver diseases such as liver cirrhosis, hepatocellular carcinoma and liver failure, and thus, it represents a therapeutic target for the treatment of these conditions. This book therefore describes the role of RAS in the pathological and pharmacological characteristics of chronic liver diseases and includes advances in signaling pathways, biomarkers and associated events that are related to RAS, such as enhanced liver fibrosis, oxidative stress and inflammation. Alterations in RAS are also known to induce multiple lung diseases, including idiopathic pulmonary fibrosis, sarcoidosis, pulmonary hypertension, acute respiratory distress syndrome and lung cancer. It is thus important to describe RAS signaling pathways, molecular and cellular mechanisms in lung disease as well as role of this system in lung fibroblast and extracellular matrix production. In addition, the inhibition of RAS as an effective treatment of lung disorders is included in this book.

This book on the status of The Renin Angiotensin System in Cancer, Lung, Liver and Infectious Diseases has been assembled to consist of 24 chapters by highly productive investigators with expertise in the field of RAS in health and disease. It mainly deals with the pathophysiology and pharmacotherapy of various health hazards such as cancer, lung, liver, kidney and infectious diseases with respect to the involvement RAS. Particularly, the mechanisms such as inflammation, oxidative stress and signal transduction related to Ang-receptors have been discussed. All the information contained in this book has been arranged into three parts: Part I— contains six chapters on the general implications of RAS in health and disease; Part II—consists of eight chapters concerning the involvement of RAS in lung, liver and kidney ailments; and Part III—contains ten chapters, which are devoted to discussions regarding the role of RAS in the pathogenesis and therapy of different types of cancer. It is our contention that the information contained in this book will not only stimulate several biomedical and clinical investigators to carry out future research to understand the involvement of RAS in the genesis of diverse diseases, but will also help in identifying various targets for drug development. Furthermore, the state-of-the-art information regarding the molecular and cellular mechanisms in this book will be useful to graduate students, postdoctoral fellows, residents and health professionals for enhancing their careers in medical research and improving the scientific basis for the practice of medicine.
We are grateful to various members of the Advisory Board for this series on “Advances in Biochemistry in Health and Disease” for their valuable suggestions. The enthusiastic support of all contributors for preparing different chapters in this book is highly appreciated. We are indeed thankful to Dr. Gonzalo Cordova for his time and efforts in evaluating and approving this project. Our cordial thanks to the St. Boniface Hospital Albrechtsen Research Centre for providing infrastructural support for this project. We also wish to express our gratitude to Mr. Rajan Muthu and his team for their efforts in the production of this book.

Winnipeg, Canada Sukhwinder K. Bhullar
Paramjit S. Tappia Naranjan S. Dhalla