scholarly journals Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2

2020 ◽  
Vol 7 ◽  
Author(s):  
Francesca Salamanna ◽  
Melania Maglio ◽  
Maria Paola Landini ◽  
Milena Fini
Keyword(s):  
Multiple Organ ◽  
Host Cells ◽  
Specific Patient ◽  
Angiotensin Converting Enzyme 2 ◽  
Body Distribution ◽  
Organ Failures ◽  
Personalized Approach ◽  
Potential Interactions

The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought the role of the angiotensin converting enzyme 2 (ACE2) back into the scientific limelight. Since SARS-CoV-2 must bind the ACE2 for entering the host cells in humans, its expression and body localization are critical to track the potential target organ of this infection and to outline disease progression and clinical outcomes. Here, we mapped the physiological body distribution, expression, and activities of ACE2 and discussed its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs. We highlighted that despite during SARS-CoV-2 infection ACE2-expressing organs may become direct targets, leading to severe pathological manifestations, and subsequent multiple organ failures, the exact mechanism and the potential interactions through which ACE2 acts in these organs is still heavily debated. Further scientific efforts, also considering a personalized approach aimed to consider specific patient differences in the mutual interactions ACE2-SARS-CoV-2 and the long-term health effects associated with COVID-19 are currently mandatory.

scholarly journals Pediatric Antiphospholipid Syndrome: from Pathogenesis to Clinical Management

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Silvia Rosina ◽  
Cecilia Beatrice Chighizola ◽  
Angelo Ravelli ◽  
Rolando Cimaz
Keyword(s):  
Antiphospholipid Syndrome ◽  
Fluid Phase ◽  
Multiple Organ ◽  
Clinical Settings ◽  
Glycoprotein I ◽  
Long Term Follow Up ◽  
Pediatric Populations ◽  
Cellular Components

Abstract Purpose of Review Elucidating the pathogenic mechanisms mediated by antiphospholipid antibodies (aPL) might exert important clinical implications in pediatric antiphospholipid syndrome (APS). Recent Findings aPL are traditionally regarded as the main pathogenic players in APS, inducing thrombosis via the interaction with fluid-phase and cellular components of coagulation. Recent APS research has focused on the role of β2 glycoprotein I, which bridges innate immunity and coagulation. In pediatric populations, aPL should be screened in appropriate clinical settings, such as thrombosis, multiple-organ dysfunction, or concomitant systemic autoimmune diseases. Children positive for aPL tests often present non-thrombotic non-criteria manifestations or asymptomatic aPL positivity. In utero aPL exposure has been suggested to result in developmental disabilities, warranting long-term follow-up. Summary The knowledge of the multifaceted nature of pediatric APS should be implemented to reduce the risk of underdiagnosing/undertreating this condition. Hopefully, recent pathogenic insights will open new windows of opportunity in the management of pediatric APS.

scholarly journals The Role of MSC Therapy in Attenuating the Damaging Effects of the Cytokine Storm Induced by COVID-19 on the Heart and Cardiovascular System

2020 ◽  
Vol 7 ◽  
Author(s):  
Georgina M. Ellison-Hughes ◽  
Liam Colley ◽  
Katie A. O'Brien ◽  
Kirsty A. Roberts ◽  
Thomas A. Agbaedeng ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Cardiovascular Complications ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Cell Therapies ◽  
Tissue Repair And Regeneration ◽  
Global Pandemic ◽  
Organ Systems

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has led to 47 m infected cases and 1. 2 m (2.6%) deaths. A hallmark of more severe cases of SARS-CoV-2 in patients with acute respiratory distress syndrome (ARDS) appears to be a virally-induced over-activation or unregulated response of the immune system, termed a “cytokine storm,” featuring elevated levels of pro-inflammatory cytokines such as IL-2, IL-6, IL-7, IL-22, CXCL10, and TNFα. Whilst the lungs are the primary site of infection for SARS-CoV-2, in more severe cases its effects can be detected in multiple organ systems. Indeed, many COVID-19 positive patients develop cardiovascular complications, such as myocardial injury, myocarditis, cardiac arrhythmia, and thromboembolism, which are associated with higher mortality. Drug and cell therapies targeting immunosuppression have been suggested to help combat the cytokine storm. In particular, mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory ability, have shown promise in early clinical studies to avoid, prevent or attenuate the cytokine storm. In this review, we will discuss the mechanistic underpinnings of the cytokine storm on the cardiovascular system, and how MSCs potentially attenuate the damage caused by the cytokine storm induced by COVID-19. We will also address how MSC transplantation could alleviate the long-term complications seen in some COVID-19 patients, such as improving tissue repair and regeneration.

scholarly journals Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein

2020 ◽  
Author(s):  
Dongchun Ni ◽  
Kelvin Lau ◽  
Frank Lehmann ◽  
Andri Fränkl ◽  
David Hacker ◽  
...  
Keyword(s):  
Structural Rearrangement ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Cryo Electron Microscopy ◽  
Monomeric Complex ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis ◽  
Viral Surface

AbstractThe human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, the role of hACE2 for virus fusion is not well understood. Blocking the transition of Spike from its prefusion to post-fusion state might be a strategy to prevent or treat COVID-19. Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. This observed hACE2 dependent dissociation of the Spike trimer suggests a mechanism for the therapeutic role of recombinant soluble hACE2 for treatment of COVID-19.

scholarly journals Angiotensin Converting Enzyme 2 in COVID-19 infections and the implications of COVID-19 on major body systems

2020 ◽  
Vol 9 (2) ◽  
pp. 78-85
Author(s):  
Malyn M.L.K. Antoine ◽  
Yancheng Xu ◽  
Rimanatou Seyni-Boureima ◽  
Chrystal Deniza Antoine-Frank ◽  
Coumba Aicha Thiam ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Uncertain Information ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Modes Of Transmission ◽  
Novel Virus ◽  
And Control ◽  
The Relationship

COVID-19, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), was first identified in China in late 2019 and since then, this disease has become a pandemic affecting many countries across the globe. Due to this outbreak, many researchers have been diligently investigating this disease for the establishment of better methods of its treatment and control. Evidence from research has led to a plethora of valuable but uncertain information on the modes of transmission of COVID-19 and the mechanisms by which SARS-CoV-2 establishes infections in targeted tissues. It is now better understood that in this disease, SARS-CoV-2 gains entrance into cells by specifically binding ACE-2 (angiotensin-converting enzyme 2); ACE-2 serves as a potential receptor for the virus. The lungs, in addition to many other organs and tissues, express ACE-2 in varying degrees. Therefore, this review will examine the role of ACE-2 in COVID-19 and the secondary effects that COVID-19 has on organs that express ACE-2. To this end, it will assist in establishing the relationship between the ACE-2 receptor and SARS-CoV-2, bringing to the forefront the correlation between the symptomatology presentation, as well as the severity of infections experienced with COVID-19. Given this, it may even provide an avenue for the generation of treatment, or create a platform for the enhanced knowledge of this novel virus, and therefore, control, and maybe unravel the mystery for long term complications.  

Twenty years of progress in angiotensin converting enzyme 2 and its link to SARS-CoV-2 disease

2020 ◽  
Vol 134 (19) ◽  
pp. 2645-2664 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Sarfaraz Ahmad ◽  
Leanne Groban
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Human Subjects ◽  
Adverse Outcomes ◽  
Converting Enzyme ◽  
Disease Evolution ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity Binding Site ◽  
Receptor Blockers

Abstract The virulence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the aggressive nature of the disease has transformed the universal pace of research in the desperate attempt to seek effective therapies to halt the morbidity and mortality of this pandemic. The rapid sequencing of the SARS-CoV-2 virus facilitated identification of the receptor for angiotensin converting enzyme 2 (ACE2) as the high affinity binding site that allows virus endocytosis. Parallel evidence that coronavirus disease 2019 (COVID-19) disease evolution shows greater lethality in patients with antecedent cardiovascular disease, diabetes, or even obesity questioned the potential unfavorable contribution of angiotensin converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers as facilitators of adverse outcomes due to the ability of these therapies to augment the transcription of Ace2 with consequent increase in protein formation and enzymatic activity. We review, here, the specific studies that support a role of these agents in altering the expression and activity of ACE2 and underscore that the robustness of the experimental data is associated with weak clinical long-term studies of the existence of a similar regulation of tissue or plasma ACE2 in human subjects.

Morphological and apoptotic changes in the intestinal mucosa and lung parenchyma after ischaemic/reperfusion injury of the jejunum

2010 ◽  
Vol 58 (2) ◽  
pp. 243-256 ◽  
Author(s):  
Ján Varga ◽  
Pavel Staško ◽  
Štefan Tóth ◽  
Zuzana Pristášová ◽  
Zuzana Jonecová ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Lung Parenchyma ◽  
Multiple Organ ◽  
Control Group ◽  
Jejunal Mucosa ◽  
Apoptotic Cells ◽  
Significant Difference ◽  
Long Term Experiment

Ischaemic/reperfusion (IR) injury of the small intestine may lead to the development of multiple organ failure. Little is known about the morphological changes occurring in the organs during the subacute course of this syndrome. The objective of this study was to observe histopathological features and the role of apoptosis in the jejunal mucosa and lung parenchyma after intestinal IR injury in a long-term experiment. Wistar rats (n = 36) were divided into 4 experimental groups (IR 10 , IR 20 , IR 30 , S). Groups IR 10 , IR 20 and IR 30 (each n = 10) were subjected to 1-hour ischaemia of the cranial mesenteric artery followed by 10, 20 or 30 days of reperfusion, respectively. The control group S (n = 6) was not subjected to ischaemia. The jejunal mucosa remained intact after all periods of reperfusion. Apoptotic cells were found particularly in the lamina propria, with the most significant difference observed in the IR 30 group (P < 0.01). The lung parenchyma had lower regenerative capacity, which was confirmed by a high index of histological damage after 30 days of reperfusion (P < 0.01) and by the presence of an increased number of apoptotic cells, especially in the pulmonary interstitium. The number of apoptotic cells was ten times higher than in the control group (P < 0.001).

scholarly journals Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 272
Author(s):  
Anna M. Fratta Pasini ◽  
Chiara Stranieri ◽  
Luciano Cominacini ◽  
Chiara Mozzini
Keyword(s):  
Potential Role ◽  
Viral Infections ◽  
Host Cells ◽  
Nuclear Factor ◽  
Angiotensin Converting Enzyme 2 ◽  
Pyrin Domain ◽  
Nrf2 Activation ◽  
Anti Inflammatory ◽  
Receptor Family

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

scholarly journals Silica Particles Trigger Pulmonary Fibrosis Act Through Cell-To-Cell Delivery of Exosomal Mir-107

2021 ◽  
Author(s):  
Di Wang ◽  
Changfu Hao ◽  
Wei Guo ◽  
Yangqing Pei ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pulmonary Fibrosis ◽  
Cell Cycle Progression ◽  
Silica Particles ◽  
Lung Fibroblasts ◽  
Targeted Inhibition ◽  
Exosomal Mirna ◽  
Potential Interactions

Abstract Background: Long-term exposure to inhalable silica particles may lead to a serious systemic pulmonary disease called silicosis. However, the role and mechanisms of exosomes in silicosis are not well understood. We previously reported that serum exosomal micro (mi) RNA profile was altered in pneumoconiosis patients and silica-exposed macrophages.This study was aimed to explore and verify the role of the exosomal miRNA in lung fibrosis when exposed to silica particles. Results: The RT-qPCR result revealed that the levels of the miR-107, miR-122-5p, miR-125a-5p, miR-126-5p, and miR-335-5p were elevated in serous exosomes of silicosis patients. A bioinformatics analysis predicted 5 potential interactions involving these miRNAs, with miR-107–cyclin-dependent kinase (CDK) 6 having the highest score. In a mouse model of silica particle-induced silicosis, miR-107 level in serum exosomes and lung tissue was increased during the development of fibrosis, while inhibition of miR-107 reduced pulmonary fibrosis. The number of exosomes secreted by macrophages exposed to silica particles was also increased and showed altered cargo composition, and showed a capacity to promote lung fibroblast transdifferentiation through a possible mechanism involving the delivery of miR-107 by macrophages to lung fibroblasts via exosomes, resulting in targeted inhibition of CDK6, reduced retinoblastoma protein phosphorylation, and inhibition of E2F1 and cell cycle progression. Conclusion: In summary, exosomal miR-107 derived from macrophages exposed to silica particles were transferred to pulmonary fibroblasts to trigger their transdifferentiation by targeting CDK6 and arresting cell cycle. These findings provide insight into the pathogenesis of silicosis and potential targets for intervention.

scholarly journals The Interplay Between COVID-19 and Cardiovascular Disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Brandon Shokoples ◽  
Nathanne S. Ferreira ◽  
Kevin Comeau
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Events ◽  
Organ Damage ◽  
Healthcare Systems ◽  
Host Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Rapid Spread ◽  
History Of

Introduction: The emergence of the global COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus, SARS-CoV-2, has created a substantial burden on healthcare systems worldwide. The systemic impacts of COVID-19 infection are severe and broad in their implications, and the cardiovascular system is no exception. Discussion: Patients with a history of cardiovascular disease are at an increased risk for hospitalization and mortality, and COVID-19 infection has now been demonstrated to initiate acute, but serious, episodes of cardiovascular events such as stroke. Considering the rapid spread of COVID-19 across the globe and the inability of healthcare systems to address and adequately respond to the pandemic, therein lies an increased need for understanding the interplay between COVID-19 infection and cardiovascular disease. SARS-CoV-2 relies on binding the angiotensin-converting enzyme-2 (ACE2) receptor to infect host cells, with ACE2 representing a critical regulator of blood pressure homeostasis and proper cardiovascular functioning. Conclusion: Identifying the exact role of ACE2 in COVID-19 infection will have major implications for understanding the disease; therefore, here we have reviewed ACE2’s involvement in the pathogenesis of COVID-19 infection and the resulting end-organ damage. In addition, we have summarized how COVID-19 affects cardiovascular physiology, and how COVID-19 infection can manifest in acute cardiovascular events. Finally, we examine why patients with cardiovascular disease are at an increased risk of succumbing to COVID-19 and what the long-term cardiovascular implications of COVID-19 infection could mean. Relevance: This paper discusses the cardiovascular consequences of the global COVID-19 pandemic.

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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