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

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