The Renin Angiotensin System in Cardiovascular Disease

Preface
Contents
Contributors
Part I Modulatory Aspects of Renin Angiotensin System
1 Renin–Angiotensin–Aldosterone System and LOX-1 Interaction in Hypertension with a Focus on Modulation of the Immune System
Introduction
Innate and Adaptive Immune Responses in Hypertension
The Interplay of LOX-1 and RAS System in Hypertension
References
2 Renin Angiotensin System and Thyroid Hormone Crosstalk: From Experimental Approaches to Clinical Perspectives
Introduction
Main Components of “Classical” Arm of RAS
Angiotensinogen
Renin
Angiotensin-Converting-Enzyme
Angiotensin II
Ang II Receptors: AT1R and AT2R
Main Components of “Protective” Arm of RAS
Thyroid Hormone and Renin Angiotensin Systems Crosstalk
Thyroid Hormone and Renin Angiotensin Systems Interaction in Some Organ Diseases
Clinical Features in Thyroid Hormone and Renin Angiotensin Systems Crosstalk
Conclusions and Perspectives
References
3 Crosstalk Between Abnormal Electrical Activity and Angiotensin II Cell Signaling in the Hyperglycemic Mammalian Heart
Introduction
Characteristics and Mechanisms of Ang II-Related Cardiac Remodeling
Ang II Receptor Activation Effects on Electrical and Mechanical Activities of the Heart Under Pathological Stimuli
Ang II-Induced Cellular and Organelle Level Alterations in Cardiomyocytes
Roles of Ang II Receptors on Structural and Electrophysiological Remodeling in Hyperglycemic Heart
Effects of Ang II Receptor Antagonists on Cardiac Remodeling in Insulin-Resistant Elders
Conclusions and Future Perspectives
References
4 Cardiovascular Physiopathology of Angiotensin II and Its Plasma and Nuclear Envelop Membranes’ Receptors
Introduction
Ang II Biosynthesis
Ang II Receptors
The AT1 Receptor
AT2 Receptor
Nuclear Targeting of Ang II Receptors
Conclusion and Perspective
References
5 Epigenetic miRNA Mediated Regulation of RAS in Cardiovascular Diseases
Introduction
Classical RAS: Mechanism of Action
The Role of Cardiac RAS in the Heart-Tissue
Epigenetics and RAS
Epigenetic miRNA Regulation of RAS in Cardiovascular Diseases
Hypertension
Myocardial Remodeling: Cardiac Hypertrophy and Fibrosis
Heart Failure
COVID-19 and the RAS
Medication
Conclusion
References
6 Epigenetics Changes in Renin Angiotensin System (RAS): Application of Biosensors for Monitoring These Changes
Introduction
Polymorphisms in the RAS Genes and Hypertension
Epigenetics and Hypertension and RAS
Biosensors and Hypertension
Conclusion and Outline
References
7 Genetic Polymorphisms in the Renin-Angiotensin-Aldosterone System
Introduction
Polymorphisms in the Gene for Renin (REN)
Polymorphisms in the Gene for Renin-Binding Protein (RENBP)
Polymorphisms of the Gene for Angiotensinogen (AGT)
Polymorphisms of the Gene for the Angiotensin-Converting Enzyme (ACE)
Polymorphisms of the Gene for Angiotensin-Converting Enzyme 2 (ACE2)
Polymorphisms of the Gene for Angiotensin Receptor 1 (AGTR1)
The Polymorphisms of the Gene for Aldosterone Synthase
Final Remarks
References
8 Mitochondria: A Key Protagonist of the Renin Angiotensin System
Introduction
RAS and Its Effect on Cardiovascular System and Kidney
Mitochondria and Mitochondrial Biogenesis
RAS and Oxidative Stress
Crosstalk Between Mitochondria and RAS
Mitochondria and Cardiovascular Diseases
Mitochondria Targeted Treatment
Conclusions
References
9 The Renin Angiotensin System at the Time of COVID-19
Some Background on RAS
COVID-19 in the Context of RAS
Association of ACE2, Lifestyle Diseases, and SARS-CoV-2
Treatment of Cardiovascular Diseases Considering COVID-19
Concluding Remarks and Future Perspective
References
Part II Pathophysiological Implications of Renin Angiotensin System
10 A Ying-Yang Perspective on the Renin Angiotensin System in Cardiovascular Disease
Introduction
Current Prospect of RAS in CVD (Systemic vs Tissue)
Ang II Generating Substrates and Enzymes in CVD
Current and Proposed Therapeutic Aspect of CVD
References
11 Central Control of Sympathetic and Renin Angiotensin System in the Development of Hypertension
Introduction
Central Sympathetic System in the Control of Blood Pressure
Modulation of Central Sympathetic System by Neuropeptide Y
Central Renin–Angiotensin–Aldosterone System (RAAS)
Interaction Between Central Sympathetic and Renin Angiotensin System
Conclusion
References
12 Role Renin Angiotensin System in Hypertension
Angiotensinogen
Angiotensin and Dysfunction
RAS—Hypertension
Central AT1R in Different Types of Hypertension
Spontaneous Hypertension
Stress Causes Hypertension
L-NAME-induced Hypertension
Renovascular Hypertension
Obesity-induced Hypertension
ANG II Causes Hypertension
Conclusions
References
13 Comparing the Influence of Angiotensin II and TGFβ1 on Cardiac Fibroblasts; Myofibroblast Plasticity and Resistance to Apoptosis
Introduction: Fibroblasts, Myofibroblasts and Cardiac Fibrosis
Myofibroblast Plasticity—The Extracellular Matrix Niche, Biomechanical Input and SKI
Biomechanical Input and Regulation of Fibroblast Phenotype
TGFβ1, Smads and SKI in Fibroblast Plasticity
Myofibroblast Evasion of Apoptosis—The Role of Angiotensin II
Conclusions
References
14 Role of Renin Angiotensin System in the Pathophysiology of Coronary Heart Disease: Advancements in Diagnosis, Therapy and Preventive Strategies
Introduction
Pathophysiological Mechanisms of CHD
Biomarkers Used in Diagnosis of CHD
MiRNAs
Advanced Glycation End Products (AGEs)
Trimethylamine-N-Oxide (TMAO)
Gamma-Glutamyl Transferase (GGT)
Pentraxins (PXT)
Myeloperoxidase (MPO)
Neopterin
Lactate Dehydrogenase (LDH)
Synthetic Drugs
Phytotherapies
Dietary Supplements
Other Treatment Strategies
Future Prospects
Concluding Remarks
References
15 Renin Angiotensin System in the Pathophysiology of Diabetic Cardiomyopathy in Type 2 Diabetes
Introduction
Diabetes-Induced Activation of the Renin Angiotensin System
Overview of the Renin Angiotensin System
Renin Angiotensin System in Type II Diabetes
Metabolic Disturbances in the Diabetic Heart
Normal Cardiac Energetics
Abnormal Cardiac Fatty Acid Uptake and Utilization in Diabetes
Defective Cardiac Glucose Uptake and Utilization in Diabetes
Cardiac Mitochondrial Oxidative Phosphorylation Impairment in Diabetes
Cardiac Remodeling in Diabetic Cardiomyopathy
Renin Angiotensin System Modulation as a Treatment of Diabetic Cardiomyopathy
AT1 Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Renin Inhibition
ACE2/Ang-(1-7)/Mas Axis Activation
Conclusion
References
16 Renin Angiotensin System and Obesity-Related Organ Damage
Renin Angiotensin System Changes in Obesity
Role of the Renin Angiotensin System in Obesity-Related Hypertension
Role of the Renin Angiotensin System in Obesity-Related Organ Damage
Renin Angiotensin System Modifications After Bariatric Surgery
Blood Pressure Changes After Bariatric Surgery. Role of the Renin Angiotensin System
Obesity-Related Organ Damage Changes After Bariatric Surgery. Role of the Renin Angiotensin System
Conclusions
References
17 Renin Angiotensin System in Aging and Regeneration
Introduction
RAS in Aging
RAS in Vascular Aging
RAS in Cardiovascular Aging
RAS in Renal Aging
RAS in Brain Aging
RAS in Skeletal Muscle Aging
RAS in Other Aging Induced Diseases
RAS Involvement in Physiological Aging
Mechanism of RAS Induced Aging
RAS in Regeneration
Conclusion
Bibliography
18 Renin Angiotensin System in the Maturation and Failure of Arterio-Venous Fistula
Introduction
Renin Angiotensin System
Renin Angiotensin System and AVF
Conclusion
References
Part III Pharmacotherapeutic Aspects of Renin Angiotensin System
19 Renin–Angiotensin–Aldosterone System as an Old New Target in Heart Failure Therapy
Rationale for Renin–Angiotensin–Aldosterone System (RAAS) Inhibition in Heart Failure (HF)
RAAS Inhibition is the Cornerstone of GDMT in HFrEF
Angiotensin-Converting Enzyme (ACE) Inhibitors
Angiotensin Receptor Blockade
Dual Angiotensin Receptor and Neprilysin Inhibition
Aldosterone Antagonists
Concerns and Limitations of RAAS Inhibition in HF
Renin Inhibition
HFmrEF
HFpEF
Coronavirus Disease 2019 (COVID-19)
Summary
References
20 Renin Angiotensin System Inhibitors in Heart Failure with Reduced Ejection Fraction: Clinical Evidence and Considerations for Use
Introduction
Renin Angiotensin System
Clinical Trials of Angiotensin-Converting Enzyme Inhibitors in HFrEF
Clinical Trials of Angiotensin II Receptor Blockers in HFrEF
Clinical Trials Comparing the Efficacy of ACE-Is and ARBs in HFrEF
Clinical Trials with Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
Selection of ACE-I versus ARB in HFrEF
Conclusions
References
21 Protective Role of the AT1 Receptor in the Heart: A Biosensor of Stress
Introduction
Role of AT1 Receptor in Cardiac Hypertrophy
Receptor Knockout Studies
Alternative Interpretations
AT1R as a Mechanosensor
β-Arrestin Biased Signaling
Nanobodies as Potential Conformation-Specific Drugs
Conclusions and Future Directions
References
22 Cardiovascular Protective Arm of Renin Angiotensin System
Introduction
Angiotensin-Converting Enzyme-2 (ACE2)
Angiotesnin-(1–7)
Angiotesnin-(1–9)
Alamandine
Conclusions
References
23 Quercetin: A Promising Flavonoid for the Therapy of Cardiac Hypertrophy and Heart Failure Mediated by the Renin Angiotensin System
Introduction
Relationship of RAS with the Pathogenesis of Cardiac Hypertrophy and Heart Failure
Biomarkers Involved in CVDs
Quercetin as a Promising Cardioprotective Agent
Chemistry and Structure-Activity Relationship (SAR) of Quercetin
Dietary Sources and Biological Properties of Quercetin
Cellular and Molecular Pharmacological Mechanisms of Quercetin
Promising Therapeutic Applications of Quercetin
Recent Advances in the Management of Cardiac Hypertrophy and Congestive Heart Failure
Molecular Mechanisms of Quercetin in Improving CVDs Mediated by RAS
Targeting the Mechanism of Action Quercetin for Heart Failure
Role of Quercetin in RAS Induced Cardiac Hypertrophy
Preclinical and Clinical Studies Done with Quercetin
Quercetin Containing Dietary Supplements Marketed for Treating Different Ailments
Opportunities and Challenges of Quercetin Therapy
Discussion and Future Prospects
Conclusions
References
24 H2S Signals and Renin Angiotensin System in Cardiovascular Diseases
Introduction
Enzymatic Pathways of Endogenous H2S Generation and Its Cardioprotective Roles
The RAS in Cardiac Dysfunctions
Interplay of H2S Signals and RAS in CVDs
Hypertension
Cardiac Hypertrophy
Cardiac Fibrosis
Heart Failure
Atherosclerosis
Aortic Aneurysms
Endothelial Dysfunctions
H2S as ACE Inhibitors
Conclusion and Perspectives
References
25 Emerging Role of ACE-2 in Cerebrovascular and Neurological Disorders: Lessons Learnt from COVID-19
Introduction
Cardiovascular Disorders and ACE-2
Cerebrovascular Disorders and ACE-2
Neurological Disorders and ACE-2
COVID-19 and ACE-2
Conclusions
References
Index