scholarly journals Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System? A Call for Epidemiologic Investigations

2020 ◽  
Vol 71 (15) ◽  
pp. 870-874 ◽  
Author(s):  
Thomas C Hanff ◽  
Michael O Harhay ◽  
Tyler S Brown ◽  
Jordana B Cohen ◽  
Amir M Mohareb
Keyword(s):  
Cardiovascular Disease ◽  
Research Priorities ◽  
Renin Angiotensin System ◽  
Fulminant Myocarditis ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
System A ◽  
Ras Inhibition

Abstract Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

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.

C. The renin-angiotensin system. A history and review of the renin-angiotensin system

1969 ◽  
Vol 173 (1032) ◽  
pp. 317-325 ◽  
Keyword(s):  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Blood Stream ◽  
Biologically Active ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System A ◽  
Aldosterone Production ◽  
Pressor Agent

An outline of the development of knowledge of the renin-angiotensin system is given, and the nature of the enzyme renin, its site within the kidney as well as in other organs, and its action on plasma substrate to form first the decapeptide which is converted to the biologically active octapeptide, are considered. The methods of measurement of renin and angiotensin in body fluids are discussed and the factors causing increased or decreased secretion of renin into the blood stream related to physiological and pathological situations. The role of angiotensin as a pressor agent, vasoconstrictor and stimulator of aldosterone production is assessed in the light of current knowledge.

scholarly journals Interactions of Renin-Angiotensin System and COVID-19: The Importance of Daily Rhythms in ACE2, ADAM17 and TMPRSS2 Expression

2021 ◽  
pp. S177-S194
Author(s):  
J ZLACKÁ ◽  
K STEBELOVÁ ◽  
M ZEMAN ◽  
I HERICHOVÁ
Keyword(s):  
Renin Angiotensin System ◽  
Positive Association ◽  
Ang Ii ◽  
Virus Envelope ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Circadian Control ◽  
A Disintegrin And Metalloproteinase

Angiotensin-converting enzyme 2 (ACE2) was identified as a molecule that mediates the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several membrane molecules of the host cell must cooperate in this process. While ACE2 serves in a membrane receptor-mediating interaction with the surface spike (S) glycoprotein of SARS-CoV-2 located on the virus envelope, enzyme A disintegrin and metalloproteinase 17 (ADAM17) regulates ACE2 availability on the membrane and transmembrane protease serine 2 (TMPRSS2) facilitates virus-cell membrane fusion. Interestingly, ACE2, ADAM17 and TMPRSS2 show a daily rhythm of expression in at least some mammalian tissue. The circadian system can also modulate COVID-19 progression via circadian control of the immune system (direct, as well as melatonin-mediated) and blood coagulation. Virus/ACE2 interaction causes ACE2 internalization into the cell, which is associated with suppressed activity of ACE2. As a major role of ACE2 is to form vasodilatory angiotensin 1-7 from angiotensin II (Ang II), suppressed ACE2 levels in the lung can contribute to secondary COVID-19 complications caused by up-regulated, pro-inflammatory vasoconstrictor Ang II. This is supported by the positive association of hypertension and negative COVID-19 prognosis although this relationship is dependent on numerous comorbidities. Hypertension treatment with inhibitors of renin-angiotensin system does not negatively influence prognosis of COVID-19 patients. It seems that tissue susceptibility to SARS-CoV-2 shows negative correlation to ACE2 expression. However, in lungs of infected patient, a high ACE2 expression is associated with better outcome, compared to low ACE2 expression. Manipulation of soluble ACE2 levels is a promising COVID-19 therapeutic strategy.

ACE2 in the renin–angiotensin system

2020 ◽  
Vol 134 (23) ◽  
pp. 3063-3078 ◽  
Author(s):  
Thiago Verano-Braga ◽  
Ana Luiza Valle Martins ◽  
Daisy Motta-Santos ◽  
Maria José Campagnole-Santos ◽  
Robson Augusto Souza Santos
Keyword(s):  
Recent Literature ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Critical Component ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Critical View ◽  
Renin Angiotensin ◽  
20Th Anniversary

Abstract In 2020 we are celebrating the 20th anniversary of the angiotensin-converting enzyme 2 (ACE2) discovery. This event was a landmark that shaped the way that we see the renin–angiotensin system (RAS) today. ACE2 is an important molecular hub that connects the RAS classical arm, formed mainly by the octapeptide angiotensin II (Ang II) and its receptor AT1, with the RAS alternative or protective arm, formed mainly by the heptapeptides Ang-(1-7) and alamandine, and their receptors, Mas and MrgD, respectively. In this work we reviewed classical and modern literature to describe how ACE2 is a critical component of the protective arm, particularly in the context of the cardiac function, coagulation homeostasis and immune system. We also review recent literature to present a critical view of the role of ACE2 and RAS in the SARS-CoV-2 pandemic.

SARS-CoV-2 – the Hidden Agonist of the Pressor Arm Within the Renin-Angiotensin System: Considerations for Statins and Propionate Derivatives

2021 ◽  
Vol 1 (1) ◽  
pp. 131-138
Author(s):  
Cosmin Andrei Cismaru ◽  
Gabriel Laurențiu Cismaru ◽  
Claudia Cristina Burz ◽  
Andreea Nutu ◽  
Ioana Berindan Neagoe
Keyword(s):  
Cardiovascular Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Physiological Mechanisms ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Ras Blockers

"Coronavirus disease 2019 (COVID-19) has become a serious healthcare problem, causing more than 2 million fatalities worldwide. Several treatments used for the management of chronic diseases such as hypertension, cardiovascular disease, diabetes and arthritis were shown to increase the expression of the receptor exploited by the virus, the angiotensin-converting enzyme 2 (ACE2), in vitro. This raises concerns on the safety of continuing such drugs or switching to other classes that don’t interfere with the receptor exploited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we emphasize the mechanisms behind the regulation of ACE2 expression by several widely used drugs with possible interactions with COVID-19. Moreover, we discuss how the physiological mechanisms of attenuating inflammation and fibrosis can lead to increased expression of the receptor exploited by the virus and how this expression is further influenced be statins, propionate derivative nonsteroidal antiinflamatory drugs (NSAIDs) and renin-angiotensin system (RAS) blockers."

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.

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