scholarly journals The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice

2022 ◽  
Author(s):  
Xiaoliang Jiang ◽  
Huadong Li ◽  
Yong Liu ◽  
Linlin Bao ◽  
Lingjun Zhan ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Antihypertensive Drugs ◽  
Renin Angiotensin System ◽  
Cardiac Biomarkers ◽  
Inflammation Markers ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor ◽  
Cardioprotective Effects ◽  
Heart Injury

AbstractAngiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.

Expression of an angiotensin-(1–7)-producing fusion protein produces cardioprotective effects in rats

2004 ◽  
Vol 17 (3) ◽  
pp. 292-299 ◽  
Author(s):  
Robson A. S. Santos ◽  
Anderson J. Ferreira ◽  
Ana Paula Nadu ◽  
Aline N. G. Braga ◽  
Alvair Pinto de Almeida ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Cardiac Contractility ◽  
Renin Angiotensin System ◽  
Transgenic Rats ◽  
Specific Expression ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Cardioprotective Effects ◽  
Hemodynamic Measurements

Angiotensin-(1–7) [ANG-(1–7)] is a recently described heptapeptide product of the renin-angiotensin system. Because biosynthesis of ANG-(1–7) increases in animals treated with cardioprotective drugs and inactivation of the gene for angiotensin converting enzyme 2 [an enzyme involved in the biosynthesis of ANG-(1–7)] leads to the development of cardiac dysfunction, it has been suggested that ANG-(1–7) has cardioprotective properties. To directly test this possibility, we have generated transgenic rats that chronically overproduce ANG-(1–7) by using a novel fusion protein methodology. TGR(A1–7)3292 rats show testicular-specific expression of a cytomegalovirus promoter-driven transgene, resulting in a doubling of circulating ANG-(1–7) compared with nontransgenic control rats. Radiotelemetry hemodynamic measurements showed that transgenic rats presented a small but significant increase in daily and nocturnal heart rate and a slight but significant increase in daily and nocturnal cardiac contractility estimated by dP/d t measurements. Strikingly, TGR(A1–7)3292 rats were significantly more resistant than control animals to induction of cardiac hypertrophy by isoproterenol. In addition, transgenic rats showed a reduced duration of reperfusion arrhythmias and an improved postischemic function in isolated Langendorff heart preparations. These results support a cardioprotective role for circulating ANG-(1–7) and provide a novel tool for evaluating the functional role of ANG-(1–7).

scholarly journals Covid-19: the renin–angiotensin system imbalance hypothesis

2020 ◽  
Vol 134 (11) ◽  
pp. 1259-1264 ◽  
Author(s):  
Katharina Lanza ◽  
Lucas G. Perez ◽  
Larissa B. Costa ◽  
Thiago M. Cordeiro ◽  
Vitria A. Palmeira ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Renin Angiotensin System ◽  
Disease Course ◽  
Ang Ii ◽  
Cellular Mechanisms ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Mas Receptor

Abstract The emergency of SARS-CoV-2 in China started a novel challenge to the scientific community. As the virus turns pandemic, scientists try to map the cellular mechanisms and pathways of SARS-CoV-2 related to the pathogenesis of Coronavirus Disease 2019 (Covid-19). After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin–angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19. In this perspective, we discuss potential mechanisms and evidence on this hypothesis.

Epochs in the depressor/pressor balance of the renin–angiotensin system

2016 ◽  
Vol 130 (10) ◽  
pp. 761-771 ◽  
Author(s):  
Katrina M. Mirabito Colafella ◽  
Lucinda M. Hilliard ◽  
Kate M. Denton
Keyword(s):  
Extracellular Fluid ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Mas Receptor ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

The renin–angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7) [Ang(1–7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.

scholarly journals ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good

2011 ◽  
Vol 300 (4) ◽  
pp. R804-R817 ◽  
Author(s):  
Ping Xu ◽  
Srinivas Sriramula ◽  
Eric Lazartigues
Keyword(s):  
Neurological Diseases ◽  
Renin Angiotensin System ◽  
Transgenic Animals ◽  
Angiotensin Iv ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor ◽  
Angiotensin Peptides ◽  
The Central Nervous System

The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1–7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT1 receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1–7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1–12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1–7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.

Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin Angiotensin System

2017 ◽  
Vol 24 (9) ◽  
Author(s):  
Albena Nunes-Silva ◽  
Guilherme Carvalho Rocha ◽  
Daniel Massote Magalhaes ◽  
Lucas Neves Vaz ◽  
Marcelo Henrique Salviano de Faria ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

scholarly journals Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors

2020 ◽  
Vol 9 (11) ◽  
pp. 3472 ◽  
Author(s):  
Elena-Mihaela Cordeanu ◽  
Lucas Jambert ◽  
Francois Severac ◽  
Hélène Lambach ◽  
Jonathan Tousch ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Severe Pneumonia ◽  
University Hospital ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Previously Treated ◽  
The Impact ◽  
Harmful Effects ◽  
Observation Period

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

scholarly journals ACE2: the molecular doorway to SARS-CoV-2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Miriam Marlene Medina-Enríquez ◽  
Sandra Lopez-León ◽  
José Alberto Carlos-Escalante ◽  
Zuleika Aponte-Torres ◽  
Angelica Cuapio ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Cell Types ◽  
Negative Regulator ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Functional Activities ◽  
Pathological Conditions ◽  
Organ Systems ◽  
Different Cell Types ◽  
Functional Receptor

AbstractThe angiotensin-converting enzyme 2 (ACE2) is the host functional receptor for the new virus SARS-CoV-2 causing Coronavirus Disease 2019. ACE2 is expressed in 72 different cell types. Some factors that can affect the expression of the ACE2 are: sex, environment, comorbidities, medications (e.g. anti-hypertensives) and its interaction with other genes of the renin-angiotensin system and other pathways. Different factors can affect the risk of infection of SARS-CoV-2 and determine the severity of the symptoms. The ACE2 enzyme is a negative regulator of RAS expressed in various organ systems. It is with immunity, inflammation, increased coagulopathy, and cardiovascular disease. In this review, we describe the genetic and molecular functions of the ACE2 receptor and its relation with the physiological and pathological conditions to better understand how this receptor is involved in the pathogenesis of COVID-19. In addition, it reviews the different comorbidities that interact with SARS-CoV-2 in which also ACE2 plays an important role. It also describes the different factors that interact with the virus that have an influence in the expression and functional activities of the receptor. The goal is to provide the reader with an understanding of the complexity and importance of this receptor.

Sign in / Sign up

Export Citation Format

Share Document