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.
Author(s): Sukhwinder K. Bhullar, Paramjit S. Tappia, Naranjan S. Dhalla
Series: Advances in Biochemistry in Health and Disease, 25
Publisher: Springer
Year: 2023
Language: English
Pages: 498
City: Cham
Preface
Contents
Contributors
Part I General Implications of RAS in Infectious and Other Diseases
1 Implications of Renin-Angiotensin System in Health and Disease
Introduction
Functional Components of RAS as Targets for Pharmacologic Manipulation
Involvement of RAS in Liver Disease
Involvement of RAS in Respiratory Syndrome Coronavirus Infection
Participation and Significance of RAS in Heart Failure
Concluding Remarks
References
2 The Interplay of the Renin-Angiotensin System and Solid Organ Transplantation
Introduction
Complications of Solid Organ Transplantation
Recent Efforts to Mitigate IRI
Historical Perspective of the RAS
Renin-Angiotensin System (RAS) Molecular Mechanisms
RAS in Liver Disease
OLT Modulates RAS
RAS and Alterations in Immune Pathways and Gut Microbiome
RAS/Microbiome in Health and Disease
Future Considerations
Conclusion
References
3 Correlation Between Renin Angiotensin System and Infectious Disease
Renin Angiotensin System (RAS)
Classical Pathway RAS
Non-classical Pathway RAS
Renin
ACE
ACE2
Angiotensin II
Ang (1–9), Ang (1–7)
RAS-Acting Pharmacological Agents
RAS and Infectious Lung Disease
RAS Dysfunction and Development of Acute Lung Injury (ALI)
Role of RAS in ALI Caused by Avian Influenza Virus Infections H5N1 e N7N9
Hand, Foot and Mouth Disease (HFMD)
Role of RAS in ALI Caused by SARS-CoV Coronavirus Infections
Role of RAS in ALI Caused by Coronavirus Infections SARS-CoV-2
Could A Pharmacological Approach That Modulates the RAS be of Clinical Benefit to Combat Lung Damage from Respiratory Infections?
Conclusions
References
4 Emerging Contributions of Endocrine Pathophysiology in Virus-Related Infectious Disease: Focus on the RAAS in COVID-19 and HIV
Introduction
Understanding the RAAS in Health and Dysregulated States
Traditional Use of RAAS Blockers
Where SARS-CoV-2 and HIV Meet
SARS-CoV-2 and the RAAS
RAAS Dysregulation and Organ Dysfunction in COVID-19
Therapeutic Targets and Trials in COVID-19
Future Directions in COVID-19
HIV and the RAAS
RAAS Dysregulation and Organ Dysfunction in HIV
Therapeutic Targets and Trials in HIV
Future Directions in HIV
Conclusion
References
5 Understanding the Renin-Angiotensin System in Coronavirus Disease 2019
Introduction
Angiotensin-Converting Enzyme
RASS Pathway
Hypertension
SARS-COV-2 and ACE2 in Lungs
SARS-COV-2 and ACE2 in Heart
Other Organs and Tissue Injuries
Pancreas
Skeletal Muscles
Central Nervous System
Blood Vessels
Potential Targets and Drugs
Inaccuracies and a Strong Urge to Act
Conclusion
References
6 Metabolomics Approach in Differentiating RAS Responses in ARDS and SAR-CoV-2
Introduction
SARS-CoV-2 Interaction with the RAS
Application of RAS Components in Relation to SARS-CoV-2-Related Morbidities
RAS Components as Clinical Biomarkers in SARS-CoV-2
Metabolomic Approaches to Study SARS-CoV-2
Metabolomics of RAS in SARS-CoV-2
RAS Changes in Patients with Sepsis and ARDS
RAS Metabolomics for ARDS
RAS Modulators in the Treatment of Diseases
AngII in Sepsis
Soluble ACE2
Conclusion
References
Part II Lung, Liver and Kidney Diseases
7 A Comprehensive Review of the Impact of the Renin Angiotensin System in the Liver, Lung, Infectious Diseases and Cancers
Introduction
Epidemiology of Liver, Lung, Infectious Diseases and Cancers Globally
Renin Angiotensin Aldosterone System [RAAS] Pathways
Liver Diseases
Renin Angiotensin System in Liver Disease
The Role of Renin Angiotensin System in Pathophysiological Conditions Involving the Liver
Lung Diseases
Pulmonary Renin Angiotensin System
Renin Angiotensin System in Pulmonary fibrosis
Role of Pharmacological Agents: ACE Inhibitors or ATI Receptor Blockers
Infectious Diseases
Renin Angiotensin System in Infectious Disease
Cancers
Cancer Stem Cells and Role in Pathogenesis of Cancer
Renin-Angiotensin System in Cancers
References
8 Changes in Renin Angiotensin System (RAS) in Cancers and Lung Diseases: Application of Biosensors for Monitoring These Changes
Introduction
Cancer in Canada
RAS and Cancer
Genetic and Epigenetic Factors Regulating RAS in Lung Disease
Genetic Factors
Epigenetic Factors
Epigenetic Regulation of ACE2
Biosensors
References
9 Bioinformatics Study on Renin Angiotensin in Lung, and Liver Cancer Using Plant-Based Extracts
Introduction
Liver Cancer—Hepatocellular Carcinoma
Lung Cancer
Angiotensin Converting Enzyme Inhibitors (ACEI)
Hypertension
Post Myocardial Infarction (MI)
Heart Failure
Diabetes
Chronic Kidney Disease (CKD)
Proteinuria or Nephrotic Syndrome
Post-transplant Glomerulonephritis
Bioinformatics Study on Angiotensin Enzymes in Liver and Lung Cancer
Bioinformatic Tools Used in Lung Cancer
Bioinformatic Tools Used in Liver Cancer
Plant Extracts for Treating ACE in Liver and Lung Cancer
Plant Extracts for Treating ACE in HCC
Plant Extracts for Treating ACE in Lung Cancer
Bioinformatics Work Using Plant Extracts for Treating Lung and Liver Cancer
Conclusion
References
10 Role of Renin-Angiotensin System in the Pathogenesis and Progression of Non-alcoholic Fatty Liver
Introduction
RAS
Ang II
Other Angiotensins
The Two Arms of the RAS
The Pathogenesis of NAFLD
Lipotoxicity
IR
Mitochondrial Dysfunction and Oxidative Stress
Adipocytokine Imbalance and Inflammation
Endoplasmic Reticulum Stress
Genetic Factors
The Role of RAS in NAFLD
The Role of RAS in the Development of IR and Lipogenesis
The Role of RAS in Promoting Hepatic Oxidative Stress, Inflammation, and Fibrosis
Role of RAS in ER Stress
The Potential Therapeutic Efficacy of RASi in the Treatment of NAFLD
Conclusion
References
11 The Classical and Nonclassical Renin-Angiotensin-Aldosterone System in Liver Cirrhosis
Introduction
Physiology Considerations
Liver Cirrhosis. Prorenin and Renin Regulation by Extracellular Calcium
Liver Cirrhosis. Endopeptidases and Peptides of RAAS Are Protagonists in Chronic Liver Disease and Its Renal Complications
Liver Cirrhosis. Receptors of Angiotensins and Post-receptor Mechanisms of Disease
Liver Cirrhosis. Secondary Aldosteronism, Renal Sodium Retention and Progression of Liver Fibrosis
Liver Cirrhosis. Aminopeptidases and Chronic Liver Disease
Conclusions
References
12 Renin-Angiotensin-Aldosterone System Role in Organ Fibrosis
Introduction
Renin-Angiotensin-Aldosterone System (RAAS)
Components of the RAAS System (Fig. 12.1)
Renin-Angiotensin-Aldosterone System (RAAS) Role in Fibrosis
Causes of Liver and Lung Fibrosis
Local Renin-Angiotensin-Aldosterone System (RAAS)
ACE-2 Protective Role in Liver and Lung Fibrosis
Role of Angiotensin-Converting Enzyme 2 (ACE2) in COVID-19
Signal Transduction Pathway
Targeting the RAAS in Fibrosis
Transforming Growth Factor (TGF-β)
Syndecans Amplifying the Angiotensin II and TGFβ1 Signaling
Targeting Wingless-Integrated/β-Catenin (WNT/β-Catenin) Signaling Pathway
Canonical WNT Signaling
YAP/TAZ Signaling
YAP/TAZ in Lung and Liver Fibrosis (Fig. 12.6)
Adrenergic Receptor
α-2 Adrenergic Receptor (AR) in Liver Fibrosis and Antifibrotic Effect of the α2-AR Blockers
Metabolic Processes
Metabolic Signature of Fibrosis
Metabolic Disturbance in Fibrosis Disease
Fibrosis and Lipid Metabolism
Targeting Metabolic Pathways for Fibrosis Therapy
Conclusion
References
13 Role of Renin Angiotensin-Aldosterone System in Kidney Homeostasis
Introduction
Renin Angiotensin Aldosterone System
Renin Angiotensin Aldosterone System Components
Role of Renin Angiotensin Aldosterone System in Body
Role of Renin Angiotensin Aldosterone System in Kidney
Inhibitors of RAAS Pathway
Mechanism of Inhibition
Types of Inhibitors
Combination Therapy
Inhibitors Efficacy
Conclusion
References
14 Renin-Angiotensin System in Chronic Kidney Disease: Implications in Stroke Outcome
Introduction
Epidemiology
Pre-clinical and Translational Studies Relating CKD and Stroke: RAAS Regulation
Various Clinical Reports
Conclusion
References
Part III Pathogenesis and Pharmacotherapy During Development of Cancer
15 The Renin-Angiotensin System and Cancer
Introduction
Models of Cancer
The Renin-Angiotensin System
The Systemic Renin-Angiotensin System
The Local Paracrine Renin-Angiotensin System
Renin-Angiotension System in Cancer
Epidemiological Evidence of the Role of the Renin- Angiotensin System in Cancer
In Vitro and In Vivo Evidence of the Role of the Renin- Angiotensin System in Cancer
Cancer Stem Cells Express Components of the Renin- Angiotensin System
“Bypass Loops” of the Renin-Angiotension System and Convergent Signaling Pathways
Cathepsins B, D and G
Pro-Renin Receptor and Wnt/β-Catenin
NADPH Oxidase
NF-κB Signaling
COX-2
The Renin-Angiotensin System and the Tumor Microenvironment
Cancer Stem Cells and the Tumor Microenvironment
The Renin-Angiotensin System and the Tumor Microenvironment
Therapeutic Targetting of the Renin-Angiotension System
Modulation of the Renin-Angiotensin System in the Treatment of Infantile Hemangioma
Modulation of the Renin-Angiotensin System, Its “Bypass Loops” and Convergent Signaling Pathways
Clinical Trials on the Use of Renin-Angiotensin System Inhibitors in Cancer
Conclusion
References
16 Renin-Angiotensin System and Cancer: From Laboratory to Clinics
Introduction
RAS and Tumor Progression
RAS and Cell Proliferation
RAS and Tumor Angiogenesis
RAS and Tumor Metastasis
RAS and Cell Apoptosis
Angiotensin-(1-7) and Tumor Progression
Regulation of RAS in Clinical Utilization
Angiotensin-Converting Enzyme Inhibitors (ACEIs)
AT1R Blockers (ARB)
Clinical Study of ACEI/ARB
Conclusion
References
17 Role of Renin-Angiotensin System in Cancer Cachexia
Introduction
Pathophysiology of Cancer Cachexia
Renin-Angiotensin System (RAS)
Angiotensin II
Angiotensin Converting Enzyme 2 (ACE2)
Aldosterone
Conclusion
References
18 Renin Angiotensin System Activity in Different Cancers: Mechanistic Insight and Preclinical Studies
Introduction
Overview of RAS
RAS and Cancer
Role of RAS in Different Cancers
RAS and Breast Cancer
RAS and Lung Cancer
RAS and Skin Cancer
RAS and Prostate Cancer
RAS and Renal Cancer
RAS and Gynaecologic Cancers
Gastrointestinal Cancers
Conclusion
References
19 The New Dimension of the Renin-Angiotensin System in the Hallmarks of Cancer
Introduction
RAS Pathways
The Hallmarks of Cancer and RAS
Proliferative Signaling
Evading Growth Suppressors
Resisting Cell Death
Enabling Replicative Immortality
Evading Immune Destruction
Genome Instability
Inducing Angiogenesis
Cell Migration, Invasion and Metastasis
Reprogramming of Energy Metabolism
Inflammation
Senescent Cells
Unlocking Phenotypic Plasticity
Microbioma
Epigenetics
MicroRNAs That Promote Cancer
MicroRNAs Against Cancer
Antihypertensive in Cancer
Conclusions
References
20 Renin-Angiotensin System in Hematological Malignancies
Introduction
Componential Organization of RAS
RAS and Cancer: What’s Known Till Date?
RAS Signaling: Role in Oncogenesis
Hematopoietic RAS
RAS in Hematological Malignancies
RAS and Leukemia
RAS and Lymphoma
RAS and Multiple Myeloma
RAS Inhibitors as Cancer Therapy: Single or Combinatorial
Conclusion and Future Prospects
References
21 Renin Angiotensin System (RAS): The Common Thread Between Cancer and Heart Failure
Cancer: A Brief Overview
RAS Pathway: Function and Suppression
RAS: Development, Prevention, and Treatment of Breast Cancer
Cardio-Oncology: Heart Protection via RAS Inhibition
Conclusion: Patient Experiences with RAS Inhibition
Appendix
References
22 Renin-Angiotensin System: A Potential Therapeutic Target for Colorectal Cancer
Introduction
Renin-Angiotensin System-Associated Cellular Signaling Pathways in Colorectal Cancer
RAS and EGFR/MAPK in Colorectal Cancer
RAS and PI3K in Colorectal Cancer
RAS and Wnt/β-Catenin in Colorectal Cancer
Role of Renin-Angiotensin System in Colorectal Cancer
Renin-Angiotensin System in Colorectal Cancer Liver Metastasis
Renin-Angiotensin System Targeting Therapy for Colorectal Cancer
Conclusion and Future Perspectives
References
23 Anticancer Role of Natural Phenolic Acids by Targeting Angiotensin-Converting Enzyme (ACE)
Introduction
ACE as a Molecular Target in Cancer Prevention and Therapy: Regulated Cellular Mechanisms
Chemistry of Phenolic Acids
Involvement of Phenolic Acids in Chemoprevention and Therapy Through Inhibition of ACE
Ellagic Acid
Gallic Acid
Caffeic Acid
Safety Profile of Phenolic Acids in Humans
Current Bottlenecks and Future Perspectives
Conclusions
References
24 Angiotensin-(1–7): A Prospective Cancer Therapeutic
Introduction
Ang-(1–7) and Cancer in Preclinical Animal Models
Lung Cancer
Breast Cancer
Prostate Cancer
Nasopharyngeal Carcinoma
Liver Cancer
Clinical Trials in Cancer Patients Administered Ang-(1–7)
Combination Therapy with Ang-(1–7) in Preclinical Models
Clinical Trials in Cancer Patients Administered Ang-(1–7) With Standard of Care Therapy
Conclusions
References
