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.

scholarly journals ACE2: THE DOORWAY TO SARS-CoV-2

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

The 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 71 different cell types. Some factors that can affect the expression of the ACE2 are: sex, environment, lifestyles, comorbidities, medications (e.g. anti-hypertensives) and its interaction with other genes of the renin-angiotensin system and other pathways. All of these 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 has been seen to be associated 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.

scholarly journals Review: Intracardiac intracellular angiotensin system in diabetes

2012 ◽  
Vol 302 (5) ◽  
pp. R510-R517 ◽  
Author(s):  
Rajesh Kumar ◽  
Qian Chen Yong ◽  
Candice M. Thomas ◽  
Kenneth M. Baker
Keyword(s):  
Mechanism Of Action ◽  
Treatment Strategies ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
Local System ◽  
Cardiac Cells ◽  
Angiotensin System ◽  
Pathological Conditions ◽  
Cardiac Pathophysiology ◽  
Different Cell Types

The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies.

Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus1

Genome ◽  
2020 ◽  
pp. 1-14
Author(s):  
Tasnim H. Beacon ◽  
Geneviève P. Delcuve ◽  
James R. Davie
Keyword(s):  
Blood Pressure ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
Integrin Signaling ◽  
Signal Transduction Pathways ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Mechanical Signal ◽  
Ace2 Gene

The angiotensin-converting enzyme 2 (ACE2) is the receptor for the three coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2. ACE2 is involved in the regulation of the renin-angiotensin system and blood pressure. ACE2 is also involved in the regulation of several signaling pathways, including integrin signaling. ACE2 expression is regulated transcriptionally and post-transcriptionally. The expression of the gene is regulated by two promoters, with usage varying among tissues. ACE2 expression is greatest in the small intestine, kidney, and heart and detectable in a variety of tissues and cell types. Herein we review the chemical and mechanical signal transduction pathways regulating the expression of the ACE2 gene and the epigenetic/chromatin features of the expressed gene.

scholarly journals Antioxidant-based therapies for angiotensin II-associated cardiovascular diseases

2013 ◽  
Vol 304 (11) ◽  
pp. R917-R928 ◽  
Author(s):  
Erin G. Rosenbaugh ◽  
Krupa K. Savalia ◽  
Devika S. Manickam ◽  
Matthew C. Zimmerman
Keyword(s):  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
Free Radical Scavengers ◽  
Ang Ii ◽  
Cardiovascular Research ◽  
Angiotensin System ◽  
Organ Systems ◽  
Primary Effector

Cardiovascular diseases, including hypertension and heart failure, are associated with activation of the renin-angiotensin system (RAS) and increased circulating and tissue levels of ANG II, a primary effector peptide of the RAS. Through its actions on various cell types and organ systems, ANG II contributes to the pathogenesis of cardiovascular diseases by inducing cardiac and vascular hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys, sympathoexcitation, and activation of the immune system. Cardiovascular research over the past 15–20 years has clearly implicated an important role for elevated levels of reactive oxygen species (ROS) in mediating these pathophysiological actions of ANG II. As such, the use of antioxidants, to reduce the elevated levels of ROS, as potential therapies for various ANG II-associated cardiovascular diseases has been intensely investigated. Although some antioxidant-based therapies have shown therapeutic impact in animal models of cardiovascular disease and in human patients, others have failed. In this review, we discuss the benefits and limitations of recent strategies, including gene therapy, dietary sources, low-molecular-weight free radical scavengers, polyethylene glycol conjugation, and nanomedicine-based technologies, which are designed to deliver antioxidants for the improved treatment of cardiovascular diseases. Although much work has been completed, additional research focusing on developing specific antioxidant molecules or proteins and identifying the ideal in vivo delivery system for such antioxidants is necessary before the use of antioxidant-based therapies for cardiovascular diseases become a clinical reality.

scholarly journals A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro

2020 ◽  
Author(s):  
Tianshu Xiao ◽  
Jianming Lu ◽  
Jun Zhang ◽  
Rebecca I. Johnson ◽  
Lindsay G.A. McKay ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Negative Regulator ◽  
Peptidase Activity ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2

AbstractEffective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.

scholarly journals Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex

2020 ◽  
Author(s):  
Alberto Bartolomé ◽  
Jiani Liang ◽  
Pengfei Wang ◽  
David D. Ho ◽  
Utpal B. Pajvani
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Membrane Bound ◽  
Novel Target ◽  
Functional Receptor

AbstractAngiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.

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 Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alberto Bartolomé ◽  
Jiani Liang ◽  
Pengfei Wang ◽  
David D. Ho ◽  
Utpal B. Pajvani
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Membrane Bound ◽  
Novel Target ◽  
Functional Receptor

AbstractAngiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.

scholarly journals Regulation of Angiotensin-Converting Enzyme 2: A Potential Target to Prevent COVID-19?

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Hu ◽  
Lihuan Liu ◽  
Xifeng Lu
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Tissue Injury ◽  
Renin Angiotensin System ◽  
Negative Regulator ◽  
Host Cells ◽  
Converting Enzyme ◽  
Clinical Prognosis ◽  
Potential Implication ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2

The renin–angiotensin system (RAS) is crucially involved in the physiology and pathology of all organs in mammals. Angiotensin-converting enzyme 2 (ACE2), which is a homolog of ACE, acts as a negative regulator in the homeostasis of RAS. ACE2 has been proven to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic. As SARS-CoV-2 enters the host cells through binding of viral spike protein with ACE2 in humans, the distribution and expression level of ACE2 may be critical for SARS-CoV-2 infection. Growing evidence shows the implication of ACE2 in pathological progression in tissue injury and several chronic conditions such as hypertension, diabetes, and cardiovascular disease; this suggests that ACE2 is essential in the progression and clinical prognosis of COVID-19 as well. Therefore, we summarized the expression and activity of ACE2 under various conditions and regulators. We further discussed its potential implication in susceptibility to COVID-19 and its potential for being a therapeutic target in COVID-19.

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.

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