scholarly journals Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nayara Azinheira Nobrega Cruz ◽  
Lilian Caroline Gonçalves de Oliveira ◽  
Helio Tedesco Silva Junior ◽  
Jose Osmar Medina Pestana ◽  
Dulce Elena Casarini
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Renal Physiology ◽  
Converting Enzyme ◽  
Kinin System ◽  
Kidney Replacement Therapy

Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 in Wuhan, China. The etiological agent of this disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the high transmissibility of the virus led to its rapid global spread and a major pandemic (ongoing at the time of writing this review). The clinical manifestations of COVID-19 can vary widely from non-evident or minor symptoms to severe acute respiratory syndrome and multi-organ damage, causing death. Acute kidney injury (AKI) has been recognized as a common complication of COVID-19 and in many cases, kidney replacement therapy (KRT) is required. The presence of kidney abnormalities on hospital admission and the development of AKI are related to a more severe presentation of COVID-19 with higher mortality rate. The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), which is widely expressed in human organs and is especially abundant in the kidneys. A debate on the role of ACE2 in the infectivity and pathogenesis of COVID-19 has emerged: Does the high expression of ACE2 promotes higher infectivity and more severe clinical manifestations or does the interaction of SARS-CoV-2 with ACE2 reduce the bioavailability of the enzyme, depleting its biological activity, which is closely related to two important physiological systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), thereby further contributing to pathogenesis. In this review, we discuss the dual role of ACE2 in the infectivity and pathogenesis of COVID-19, highlighting the effects of COVID-19-induced ACE2 depletion in the renal physiology and how it may lead to kidney injury. The ACE2 downstream regulation of KKS, that usually receives less attention, is discussed. Also, a detailed discussion on how the triad of symptoms (respiratory, inflammatory, and coagulation symptoms) of COVID-19 can indirectly promote renal injury is primary aborded.

scholarly journals Gastrointestinal and kidney manifestations in SARS-CoV and SARS-CoV-2 infections: role of angiotensin-converting enzyme 2

2020 ◽  
Vol 25 (1) ◽  
pp. 7-20
Author(s):  
Fatemeh Maghool ◽  
◽  
Mohammad Hassan Emami ◽  
Samaneh Mohammadzadeh ◽  
Aida Heidari ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Gastrointestinal Symptoms ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Clinical Feature ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Kidney Impairment

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2020, which has a substantial structural similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the outbreak in 2003, is currently a threat to global health. Lung involvement is the principal clinical feature in infected patients but extra-pulmonary clinical presentations are also common. The reasons for the extensive involvement of other organs are not yet clear. Angiotensin-converting enzyme 2 (ACE2), the key peptide of renin–angiotensin system (RAS), has recently identified as a major receptor for the both SARS-CoV and SARS-CoV-2 that might be a main target of coronavirus infection. ACE2 is mainly expressed in the pulmonary pneumocytes, the small intestine enterocytes as well as the proximal tubule epithelial cells of the kidneys. In addition to the respiratory tract infection symptoms, the noticeable prevalence of gastrointestinal symptoms as well as kidney impairment in hospitalized infected patients highlights other routes of infection/transmission. In present review, we discussed the role of RAS with emphasis on ACE2 in the pathogenesis of SARS-CoV and SARS-CoV-2, particularly in gastrointestinal and kidney manifestations of the diseases.

scholarly journals Role of Kinins in Hypertension and Heart Failure

2020 ◽  
Vol 13 (11) ◽  
pp. 347
Author(s):  
Suhail Hamid ◽  
Imane A. Rhaleb ◽  
Kamal M. Kassem ◽  
Nour-Eddine Rhaleb
Keyword(s):  
Blood Pressure ◽  
Spontaneous Mutation ◽  
Target Organ Damage ◽  
Regulatory System ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Protective Effects ◽  
Kinin System ◽  
Downstream Signaling

The kallikrein–kinin system (KKS) is proposed to act as a counter regulatory system against the vasopressor hormonal systems such as the renin-angiotensin system (RAS), aldosterone, and catecholamines. Evidence exists that supports the idea that the KKS is not only critical to blood pressure but may also oppose target organ damage. Kinins are generated from kininogens by tissue and plasma kallikreins. The putative role of kinins in the pathogenesis of hypertension is discussed based on human mutation cases on the KKS or rats with spontaneous mutation in the kininogen gene sequence and mouse models in which the gene expressing only one of the components of the KKS has been deleted or over-expressed. Some of the effects of kinins are mediated via activation of the B2 and/or B1 receptor and downstream signaling such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and/or tissue plasminogen activator (T-PA). The role of kinins in blood pressure regulation at normal or under hypertension conditions remains debatable due to contradictory reports from various laboratories. Nevertheless, published reports are consistent on the protective and mediating roles of kinins against ischemia and cardiac preconditioning; reports also demonstrate the roles of kinins in the cardiovascular protective effects of the angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARBs).

Renin Angiotensin System, Gut-Lung Cross Talk and Microbiota. Lessons from SARS-CoV Infections

2021 ◽  
Author(s):  
Andreia Matos ◽  
Alda Pereira da Silva ◽  
Joana Ferreira ◽  
Ana Carolina Santos ◽  
Maria Clara Bicho ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cardiovascular Diseases ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Multiple Functions ◽  
Key Pathways

The two antagonistic systems of angiotensin converting enzyme (ACE)-1 and ACE-2 are in the “eye of the hurricane” of severe acute respiratory syndrome coronavirus (SARS-CoV-2). The receptor of the SARS-CoV-2 is the same as ACE-2, which causes its under-expression after binding it, followed by the internalization of the complex virus-ACE-2. ACE-2 have multiple functions with specially relevance in cardiovascular diseases. Furthermore, the non-enzymatic role of ACE-2 gives rise to a Hartnup disease, a phenocopy involving microbiota. With this chapter, we intent to explore the key pathways involved in SARS-CoV-2 infection, from the host perspective, considering our hypothesis related to transporter of neutral amino acids, which includes tryptophan precursor of serotonin and kynurenine.

Updates on coronavirus (COVID-19) and kidney

2020 ◽  
Vol 9 (4) ◽  
pp. e34-e34 ◽  
Author(s):  
Seyed Zanyar Athari ◽  
Daryoush Mohajeri ◽  
Mir Alireza Nourazar ◽  
Yousef Doustar
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitor ◽  
Case Reports ◽  
Angiotensin Receptor Blockers ◽  
Kidney Injury ◽  
Current Treatment ◽  
High Risk Group ◽  
Converting Enzyme ◽  
Renal Disorder

The severe acute respiratory syndrome (SARS) is an infectious disease developed in Wuhan, China, at first. It involves the respiratory system and other organs like kidney, gastrointestinal tract and nervous system as well. The recent reports indicated that renal disorder is prevalent in coronavirus patients. The aim of this study was to provide a review of nephropathy caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and its mechanisms. The Web of Science, Scopus, and PubMed databases were systematically searched. Articles reporting nephropathy, coronavirus disease (COVID-19), coronavirus and the renal injury were included for assessment. Study designs, contrast agents, case reports and results were assessed. Of the assessed studies, suggested mechanisms include sepsis which caused cytokine storm syndrome or perhaps direct cellular injury due to the virus. In patients who were studied, albuminuria, proteinuria, and hematuria as well as an elevation in blood urea nitrogen and serum creatinine were observed. Additionally CT scan of the kidneys showed a decrease in tissue density suggestive of inflammation and interstitial edema. On the other hand, dialysis patients are a high-risk group than the general population. The current treatment for COVID-19 in acute kidney injury includes supportive management or kidney replacement therapy. All patients need to be quarantined. An N95 fit-tested mask and protective clothing and proper equipment are necessary. Some drugs can be effective to inhibit the outcome of this infection such as lopinavir/ritonavir, remdesvir, Chloroquine phosphate, convalescent plasma, tocilizumab, ACEi/ ARBs (angiotensin-converting enzyme inhibitor/angiotensin receptor blockers), and hrsACE2 (human recombinant soluble angiotensin-converting-enzyme 2).

scholarly journals TCA Cycle and Fatty Acids Oxidation Reflect Early Cardiorenal Damage in Normoalbuminuric Subjects with Controlled Hypertension

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1100
Author(s):  
Aranzazu Santiago-Hernandez ◽  
Marta Martin-Lorenzo ◽  
Ariadna Martin-Blazquez ◽  
Gema Ruiz-Hurtado ◽  
Maria G Barderas ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Tricarboxylic Acid Cycle ◽  
Renin Angiotensin System ◽  
Roc Curves ◽  
Tca Cycle ◽  
Urinary Metabolites ◽  
Organ Damage ◽  
Fatty Acid Binding ◽  
Angiotensin System

Moderately increased albuminuria, defined by an albumin to creatinine ratio (ACR) > 30 mg/g, is an indicator of subclinical organ damage associated with a higher risk of cardiovascular and renal disease. Normoalbuminuric subjects are considered at no cardiorenal risk in clinical practice, and molecular changes underlying early development are unclear. To decipher subjacent mechanisms, we stratified the normoalbuminuria condition. A total of 37 hypertensive patients under chronic renin–angiotensin system (RAS) suppression with ACR values in the normoalbuminuria range were included and classified as control (C) (ACR < 10 mg/g) and high-normal (HN) (ACR = 10–30 mg/g). Target metabolomic analysis was carried out by liquid chromatography and mass spectrometry to investigate the role of the cardiorenal risk urinary metabolites previously identified. Besides this, urinary free fatty acids (FFAs), fatty acid binding protein 1 (FABP1) and nephrin were analyzed by colorimetric and ELISA assays. A Mann–Whitney test was applied, ROC curves were calculated and Spearman correlation analysis was carried out. Nine metabolites showed significantly altered abundance in HN versus C, and urinary FFAs and FABP1 increased in HN group, pointing to dysregulation in the tricarboxylic acid cycle (TCA) cycle and fatty acids β-oxidation. We showed here how cardiorenal metabolites associate with albuminuria, already in the normoalbuminuric range, evidencing early renal damage at a tubular level and suggesting increased β-oxidation to potentially counteract fatty acids overload in the HN range.

scholarly journals ACE2 Shedding and the Role in COVID-19

2022 ◽  
Vol 11 ◽  
Author(s):  
Jieqiong Wang ◽  
Huiying Zhao ◽  
Youzhong An
Keyword(s):  
Amino Acids ◽  
Viral Entry ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Underlying Mechanism ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Glycoprotein

Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.

scholarly journals ACE2 the Janus-faced protein – from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19

2020 ◽  
Vol 134 (7) ◽  
pp. 747-750 ◽  
Author(s):  
Rhian M. Touyz ◽  
Hongliang Li ◽  
Christian Delles
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Basic Science ◽  
Physiological Role ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Multifunctional Protein ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.

Neurohormonal regulation of renal function during development

1988 ◽  
Vol 254 (6) ◽  
pp. F771-F779 ◽  
Author(s):  
J. E. Robillard ◽  
K. T. Nakamura
Keyword(s):  
Renin Angiotensin System ◽  
Renal Hemodynamics ◽  
Renal Physiology ◽  
Fetal Life ◽  
Renal Nerve ◽  
Angiotensin System ◽  
Postnatal Maturation ◽  
Renin Angiotensin ◽  
And Function

This review summarizes current understanding of fetal renal physiology and considers the role of the neuroadrenergic system and renin-angiotensin system in controlling renal hemodynamics and function during development. Recent evidence suggests that renal innervation appears early during fetal life but is not an important modulator of renal hemodynamics and function during resting conditions in immature animals. It has also been observed that the renal hemodynamic response to renal nerve stimulation (RNS) is less in fetal and newborn animals than in adults. But contrary to previous findings in adult animals, RNS during alpha-adrenoceptor antagonism produces renal vasodilation in fetal and newborn sheep, but not in adult ewes. The role of the renin-angiotensin system (RAS) in modulating renal hemodynamics and function during prenatal and postnatal maturation is discussed. It is suggested that the RAS plays an important role in regulating blood pressure early during fetal life, whereas its influence on renal hemodynamics and function appears later during development.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1350-1367 ◽  
Author(s):  
Matthew A. Sparks ◽  
Andrew M. South ◽  
Andrew D. Badley ◽  
Carissa M. Baker-Smith ◽  
Daniel Batlle ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Experimental Models ◽  
Multiple Organ ◽  
Host Cells ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Organ Systems

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.

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