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