scholarly journals Angiotensin-(1–7) and angiotensin-(1–9): function in cardiac and vascular remodelling

2014 ◽  
Vol 126 (12) ◽  
pp. 815-827 ◽  
Author(s):  
Clare A. McKinney ◽  
Caroline Fattah ◽  
Christopher M. Loughrey ◽  
Graeme Milligan ◽  
Stuart A. Nicklin
Keyword(s):  
Renin Angiotensin System ◽  
Protective Role ◽  
Biologically Active ◽  
Cardiovascular Physiology ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Biologically Active Peptide ◽  
And Oxidative Stress

The RAS (renin–angiotensin system) is integral to cardiovascular physiology; however, dysregulation of this system largely contributes to the pathophysiology of CVD (cardiovascular disease). It is well established that AngII (angiotensin II), the main effector of the RAS, engages the AT1R (angiotensin type 1 receptor) and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodelling of the heart and vasculature, ultimately leading to the development and progression of various CVDs, including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centred on the actions of ACE2 (angiotensin-converting enzyme 2) and the resultant production of Ang-(1–7) [angiotensin-(1–7)] from AngII, antagonizes the actions of AngII via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1–9) [angiotensin-(1–9)], has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. The present review will discuss the role of the counter-regulatory RAS peptides Ang-(1–7) and Ang-(1–9) in the cardiovascular system, with a focus on their effects in remodelling of the heart and vasculature.

scholarly journals Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

2012 ◽  
Vol 216 (2) ◽  
pp. R1-R17 ◽  
Author(s):  
Robson A S Santos ◽  
Anderson J Ferreira ◽  
Thiago Verano-Braga ◽  
Michael Bader
Keyword(s):  
Renin Angiotensin System ◽  
Biologically Active ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Potential Interactions ◽  
G Protein Coupled

Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin–angiotensin system (RAS). Ang-(1–7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1–7) synthesis. This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1–7). Thus, the axis formed by ACE2/Ang-(1–7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/proliferative arm of the RAS consisting of ACE, Ang II, and AT1receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1–7) and Mas with AT1and AT2receptors.

scholarly journals Renin-Angiotensin System Inhibitors in COVID-19: Current Concepts

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kunal Mahajan ◽  
Prakash Chand Negi ◽  
Neeraj Ganju ◽  
Sachin Sondhi ◽  
Naresh Gaur ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Protective Role ◽  
Current Data ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Ras Activation ◽  
Functional Receptor ◽  
Ras Inhibitors

The functional receptor to SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is angiotensin-converting enzyme-2 (ACE-2), the same enzyme that physiologically counters the renin-angiotensin system (RAS) activation. Some researchers have questioned RAS inhibitors’ safety in COVID-19 patients since these drugs have demonstrated an increase in ACE-2 expression in preclinical studies; therefore, they may facilitate viral invasion. On the contrary, others have hypothesized a protective role of RAS inhibitors against COVID-19-associated lung injury. Overall, the data are grossly inadequate to reach any conclusion since no human trials have yet evaluated the effects of RAS inhibitors in COVID-19. We review the current data and pathophysiological mechanisms behind this intriguing interplay between the RAS inhibitors and the COVID-19.

scholarly journals Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 876
Author(s):  
Sara Chiappalupi ◽  
Laura Salvadori ◽  
Rosario Donato ◽  
Francesca Riuzzi ◽  
Guglielmo Sorci
Keyword(s):  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Molecular Target ◽  
Advanced Glycation ◽  
Angiotensin System ◽  
Major Player ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin–angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed. 

scholarly journals ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19

2020 ◽  
Vol 134 (22) ◽  
pp. 3047-3062
Author(s):  
Koichi Yamamoto ◽  
Hikari Takeshita ◽  
Hiromi Rakugi
Keyword(s):  
Skeletal Muscle ◽  
Transmembrane Protein ◽  
Renin Angiotensin System ◽  
Protective Role ◽  
Potential Contribution ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Organs ◽  
Potential Association ◽  
Entry Receptor

Abstract Angiotensin converting enzyme-2 (ACE2) is a multifunctional transmembrane protein recently recognised as the entry receptor of the virus causing COVID-19. In the renin–angiotensin system (RAS), ACE2 cleaves angiotensin II (Ang II) into angiotensin 1-7 (Ang 1-7), which is considered to exert cellular responses to counteract the activation of the RAS primarily through a receptor, Mas, in multiple organs including skeletal muscle. Previous studies have provided abundant evidence suggesting that Ang 1-7 modulates multiple signalling pathways leading to protection from pathological muscle remodelling and muscle insulin resistance. In contrast, there is relatively little evidence to support the protective role of ACE2 in skeletal muscle. The potential contribution of endogenous ACE2 to the regulation of Ang 1-7-mediated protection of these muscle pathologies is discussed in this review. Recent studies have suggested that ACE2 protects against ageing-associated muscle wasting (sarcopenia) through its function to modulate molecules outside of the RAS. Thus, the potential association of sarcopenia with ACE2 and the associated molecules outside of RAS is also presented herein. Further, we introduce the transcriptional regulation of muscle ACE2 by drugs or exercise, and briefly discuss the potential role of ACE2 in the development of COVID-19.

scholarly journals Endocrine Significance of SARS-CoV-2’s Reliance on ACE2

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Eric Lazartigues ◽  
Mirza Muhammad Fahd Qadir ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Potential Role ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Impact ◽  
The Past ◽  
And Function ◽  
Endocrine Tissues

Abstract The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

Neuromodulatory role of angiotensin-(1–7) in the central nervous system

2013 ◽  
Vol 125 (2) ◽  
pp. 57-65 ◽  
Author(s):  
Mariela M. Gironacci ◽  
Nadia A. Longo Carbajosa ◽  
Jorge Goldstein ◽  
Bruno D. Cerrato
Keyword(s):  
Renin Angiotensin System ◽  
Cardiovascular Effects ◽  
Synaptic Cleft ◽  
Neutral Endopeptidase ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
The Central Nervous System ◽  
Release Characteristic ◽  
Transporter Expression

Ang-(1–7) [angiotensin-(1–7)] constitutes an important functional end-product of the RAS (renin–angiotensin system) endogenously formed from AngI (angiotensin I) or AngII (angiotensin II) through the catalytic activity of ACE2 (angiotensin-converting enzyme 2), prolyl carboxypeptidase, neutral endopeptidase or other endopeptidases. Ang-(1–7) lacks the pressor, dipsogenic or stimulatory effect on aldosterone release characteristic of AngII. In contrast, it produces vasodilation, natriuresis and diuresis, and inhibits angiogenesis and cell growth. At the central level, Ang-(1–7) acts at sites involved in the control of cardiovascular function, thus contributing to blood pressure regulation. This action may result from its inhibitory neuromodulatory action on NE [noradrenaline (norepinephrine)] levels at the synaptic cleft, i.e. Ang-(1–7) reduces NE release and synthesis, whereas it causes an increase in NE transporter expression, contributing in this way to central NE neuromodulation. Thus, by selective neurotransmitter release, Ang-(1–7) may contribute to the overall central cardiovascular effects. In the present review, we summarize the central effects of Ang-(1–7) and the mechanism by which the peptide modulates NE levels in the synaptic cleft. We also provide new evidences of its cerebroprotective role.

scholarly journals The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function

2010 ◽  
Vol 298 (6) ◽  
pp. F1297-F1305 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Jasmina Varagic
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Therapeutic Interventions ◽  
Experimental Hypertension ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
A Site

The study of experimental hypertension and the development of drugs with selective inhibitory effects on the enzymes and receptors constituting the components of the circulating and tissue renin-angiotensin systems have led to newer concepts of how this system participates in both physiology and pathology. Over the last decade, a renewed emphasis on understanding the role of angiotensin-(1–7) and angiotensin-converting enzyme 2 in the regulation of blood pressure and renal function has shed new light on the complexity of the mechanisms by which these components of the renin angiotensin system act in the heart and in the kidneys to exert a negative regulatory influence on angiotensin converting enzyme and angiotensin II. The vasodepressor axis composed of angiotensin-(1–7)/angiotensin-converting enzyme 2/mas receptor emerges as a site for therapeutic interventions within the renin-angiotensin system. This review summarizes the evolving knowledge of the counterregulatory arm of the renin-angiotensin system in the control of nephron function and renal disease.

scholarly journals Eicosanoids and Oxidative Stress in Diabetic Retinopathy

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 520 ◽  
Author(s):  
Mong-Heng Wang ◽  
George Hsiao ◽  
Mohamed Al-Shabrawey
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Renin Angiotensin System ◽  
Microvascular Dysfunction ◽  
Microvascular Damage ◽  
Angiotensin System ◽  
Ras Activation ◽  
Long Time ◽  
And Oxidative Stress

Oxidative stress is an important factor to cause the pathogenesis of diabetic retinopathy (DR) because the retina has high vascularization and long-time light exposition. Cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes can convert arachidonic acid (AA) into eicosanoids, which are important lipid mediators to regulate DR development. COX-derived metabolites appear to be significant factors causative to oxidative stress and retinal microvascular dysfunction. Several elegant studies have unraveled the importance of LOX-derived eicosanoids, including LTs and HETEs, to oxidative stress and retinal microvascular dysfunction. The role of CYP eicosanoids in DR is yet to be explored. There is clear evidence that CYP-derived epoxyeicosatrienoic acids (EETs) have detrimental effects on the retina. Our recent study showed that the renin-angiotensin system (RAS) activation augments retinal soluble epoxide hydrolase (sEH), a crucial enzyme degrading EETs. Our findings suggest that EETs blockade can enhance the ability of RAS blockade to prevent or mitigate microvascular damage in DR. This review will focus on the critical information related the function of these eicosanoids in the retina, the interaction between eicosanoids and reactive oxygen species (ROS), and the involvement of eicosanoids in DR. We also identify potential targets for the treatment of DR.

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