Role Of Angiotensin-converting Enzyme Research Articles

Analysis of the interaction of ACE2, TMPRSS2 genes and their polymorphisms with the SARS-CoV-2 virus

Host genes act as a factor related to susceptibility and resistance to viral infections. The article provides a description of modern scientific studies devoted to the study of the role of the ACE2, TMPRSS2 genes, and their single-nucleotide polymorphisms in infection with the SARS-CoV-2 virus. SNPs of the ACE2 gene, TMPRSS2 can affect the penetration of SARS-CoV-2 into the cell. In addition, the study of these polymorphisms will determine the predisposition of an individual to the disease COVID–19, or the nature of its course. Based on the literature sources, the role of angiotensin-converting enzyme 2 and transmembrane proteases in the participation of the SARS-CoV-2 virus penetration process with the body cells is noted. Other functions that ACE2 and TMPRSS2 receptors perform in the human body are also described. The characteristics of two genes and their fairly well-known polymorphisms are given. The tissues and organs in which genes are expressed are marked. Information on the frequency of alleles of genetic variants of genes in different populations is shown. In addition to describing the relationship of gene polymorphisms with the disease caused by SARSCoV-2, information is provided on the association of these genetic variations with diseases of the blood vascular system and oncological diseases.

Covid-19 and severe OAT syndrome with dramatic recovery

We describe a young man of 37 years with a transient but marked Oligoasthenoteratozoospermia (OAT) syndrome due to severe covid infection with the perfect recovery of semen parameters along with recovery of general health. Setting district general hospital: Intervention none. We review the role of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 virus), the role of Angiotensin-Converting Enzyme 2 (ACE-2), Angiotensin 1-7 (Ang 1-7) and propose that it is potentially involved in a cause and effect mechanism of injury.

The role of membrane and circulating forms of ACE 2 in pathological processes in COVID-19 infection

The review analyzes milestone information about the function and pathogenic significance of human angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the development of diseases such as hypertension, malabsorption of certain amino acids in the intestine, and a new type of pneumonia COVID-19 caused by the SARSCoV-2 virus. Based on the latest literary sources, an assessment is made of the role of differential expression of receptor and soluble forms of this protein in the functioning of the renin-angiotensin-aldosterone system, as well as the mechanisms of ACE2 participation in the sequential chemical conversion of angiotensin II and its effect on the function of the cardiovascular system. The role of ACE2 in the development of inflammatory processes in the intestine and its effect on the composition of the intestinal microbiota are also discussed. In addition, the review presents most general data on the proteolytic activation of the S-glycoprotein of the SARS-CoV-2 virus and its participation, together with ACE2, in the process of virus introduction into the host cell. In conclusion, the hypothesis about autoimmune complications of COVID-19 associated with the formation of the S-glycoproteinACE2 immune complex and the production of autoantibodies is considered.

Elevated mid-pregnancy plasma levels of angiotensin-converting enzyme 2 in women prior to the development of preeclampsia

Preeclampsia and cardiovascular disease (CVD) share multiple features and risk factors. Circulating angiotensin-converting enzyme 2 (ACE2) is increased in CVD and mediates SARS-CoV-2 entry into host cells, causing COVID-19 infection. The role of ACE2 in preeclampsia pathophysiology is unknown. We hypothesized that circulating ACE2 is increased in mid-pregnancy in women later developing preeclampsia. We included 296 women later developing preeclampsia (cases) and 333 women with a continuous healthy pregnancy (controls). Circulating ACE2 was measured with an immunoassay based on proximity extension assay technology, with levels being expressed as relative quantification on a log2 scale. Median (interquartile range) ACE2 levels were higher in cases than in controls; 3.84 (3.50–4.24) vs. 3.72 (3.45–4.04), p = 0.002. Adjusted logistic regression models showed a 60% increased risk for later development of preeclampsia with one unit elevation of ACE2 (adjusted odds ratio (aOR) 1.60, 95% confidence intervals (CI) 1.17–2.18). Preterm preeclampsia (diagnosis before 37 gestational weeks, n = 97) seemed to have a stronger ACE2 association than term preeclampsia, n = 199 (aORs, 95% Cis 2.14, 1.15–3.96 and 1.52, 1.04–2.23, respectively). Circulating ACE2 is increased at mid-pregnancy in women later developing preeclampsia, particularly preterm preeclampsia. Thus, our finding indicates a partly shared pathophysiological pathway between preeclampsia and CVD.

Role of angiotensin-converting enzyme 2 in fine particulate matter-induced acute lung injury

Fine particulate matter (PM2.5) pollution poses significant health concerns worldwide and can cause respiratory diseases. However, how it causes health problems is still poorly understood. Angiotensin-converting enzyme (ACE)2 is a terminal carboxypeptidase implicated in the functions of renin-angiotensin system (RAS) and plays a crucial role in the control of lung inflammation. To investigate whether ACE2 functions in PM2.5-induced lung inflammation, wild-type (WT) C57BL/6J mice and ACE2 knock-out (KO) mice were intratracheally instilled with PBS or PM2.5 suspension for 3 consecutive days, respectively. The concentrations of cytokines in bronchoalveolar lavage fluid (BALF) were determined by ELISA. The expression of ACE2 and ACE and activation of inflammatory signaling pathways in lung tissues were evaluated by immunofluorescence staining and Western blotting. We found that PM2.5 exposure increased ACE2 expression. Loss of ACE2 significantly elevated the levels of total proteins, total cells, and the concentrations of MCP-1, IL-1β in BALF after PM2.5 challenge. Additionally, loss of ACE2 enhanced lung pathologies, airway resistance, and inflammatory signaling activation. Collectively, loss of ACE2 exacerbates PM2.5-induced acute lung injury in mice.

Клінічні детермінанти маніфестації коронавірусної хвороби (COVID-19)

Подано огляд сучасних публікацій, присвячених визначенню факторів, що впливають на інфікування, клінічний перебіг та наслідки коронавірусної хвороби (COVID-19). Наведено статистичні дані щодо частоти підвищеного артеріального тиску та несприятливих клінічних проявів вірусного захворювання в різних популяціях. Показано провідну роль ангіотензинперетворюючого ферменту 2 як функціонального клітинного рецептора для коронавірусу та його участь у формуванні множинних системних проявів COVID-19. Подається механізм пошкоджуючих ефектів тютюнопаління при вірусній пневмонії. Відповідно до літературних даних висвітлено взаємозв’язок між метаболічними порушеннями при ожирінні та ризиком тяжкого перебігу коронавірусної хвороби. З патофізіологічних позицій надається пояснення виникнення загрозливих ускладнень у хворих на нову коронавірусну інфекцію за наявності цукрового діабету — масивне ураження легень, гострий респіраторний дистрес-синдром, протромботичний стан, венозний та артеріальний тромбоз.

Restoration of Brain Angiotensin-Converting Enzyme 2 Alleviates Neurological Deficits after Severe Traumatic Brain Injury via Mitigation of Pyroptosis and Apoptosis.

Clinically, the renin-angiotensin-aldosterone system is activated intensely in patients with moderate to severe traumatic brain injury (TBI). Increased angiotensin II in circulatory blood after TBI can enter the brain through the disrupted blood-brain barrier. Angiotensin-converting enzyme 2 (ACE2) is an enzyme that metabolizes angiotensin II into angiotensin (1-7), which has been shown to have neuroprotective results. The expression and role of ACE2 in the brain after TBI remains elusive, however. We found that ACE2 protein abundance was downregulated around the contusional area in the brains of both humans and mice. Endogenous ACE2 was expressed in neurons, astrocytes, and microglia in the cortex of the mouse brain. Administration of recombinant human ACE2 intracerebroventricularly alleviated neurological defects after TBI in mice. Treatment of recombinant human ACE2 suppressed TBI-induced increase of angiotensin II and the decrease of angiotensin (1-7) in the brain, mitigated neural cell death, reduced the activation of NLRP3 and caspase3, decreased phosphorylation of mitogen-activated protein kinases, and nuclear factor kappa B, and reduced inflammatory cytokines tumor necrosis factor alpha and interleukin-1β. Administration of ACE2 enzyme activator diminazene aceturate intraperitoneally rescued downregulation of ACE2 enzymatic activity and protein abundance in the brain. Diminazene aceturate treatment once per day in the acute stage after TBI alleviated long-term cognitive defects and neuronal loss in mice. Collectively, these results indicated that restoration of ACE2 alleviated neurological deficits after TBI by mitigation of pyroptosis and apoptosis.

The role of angiotensin-converting enzyme 2 (ACE2) in SARS-CoV-2 (severe acute respiratory syndrome Coronavirus-2) infection process

SARS-CoV-2 can cause severe acute respiratory illness and multi-organ injury. Angiotensin-converting enzyme 2 (ACE2) is an important enzyme of the renin-angiotensin system (RAS), which is the main receptor for entry of SARS-CoV-2 into host cells. Both cell surface ACE2 and soluble ACE2 (sACE2) can interact with the receptor binding domain (RBD) in SARS-CoV-2 S protein. After binding to cell surface ACE2, SARS-CoV-2 enters host cells by direct fusion of the viral with host cell membranes with the support of host’s TMPRSS2 (transmembrane serine protease 2) and furin. In contrast, sACE2-bound SARS-CoV-2 enters host cells through AT1 (Angiotensin type 1 receptor) and AVPR1B (arginine vasopressin receptor 1B). The entery process strongly down regulates membrane-bound ACE2, promoting an activation of the canonical pathway of RAS (ACE-Ang II-AT1 receptor axis). Consequently, this promotes an intense activity of NF-kB (nuclear factor kappa B), which in turn increases the transcription of IL-6, and triggers the cytokine storm. Moreover, the decreasing of ACE2 function in lung leed to the activation of DABK/BKB1R axis signaling, contributing to the pathogenesis of acute lung inflammation. This review summarizes information about the role of ACE2 in SARS-CoV-2 infection and Covid-19, also the research directions for prevention and treatment of Covid-19 which based on ACE2.

The Role of Angiotensin-Converting Enzyme in Immunity: Shedding Light on Experimental Findings.

Angiotensin-converting enzyme (ACE) is a zinc-dependent dicarboxypeptidase with two catalytic components, which has an important role in regulating blood pressure by converting angiotensin I to angiotensin II. ACE breaks down other peptides besides angiotensin I and has a variety of physiological effects together with renal growth and reproduction in men. ACE also acts on innate and acquired immune systems by affecting macrophage and neutrophil function, and these outcomes are exacerbated due to the overexpression of ACE. Overexpression of ACE in macrophages imposes antitumor and antimicrobial response, and it enhances the ability of neutrophils to produced super peroxide that has a bactericidal effect. ACE is also known to contribute to the expression of Major Histocompatibility Complex (MHC) class I and MHC class II peptides through enzymatic alterations of these peptides. Apprehending the expression of ACE and its effects on myeloid cell (myelogenous cells) activity can be promising in therapeutic interventions, including treatment of infection and malignancy.

Angiotensin Converting Enzyme-2: A Doorway for SARS-CoV-2

: The novel coronavirus severe acute respiratory syndrome Corona Virus-2 (SARS-CoV- -2) has become a pandemic, as declared by WHO in March 2020 producing deleterious effects on patients worldwide. The angiotensin-converting enzyme-2 (ACE-2) has been recognized as the coreceptor for SARS-CoV-2 infections and may act as a therapeutic step in blocking the enzyme to reduce SARS-CoV-2 expression and further cellular entry. Presently, the role of ACE-2 in coronavirus disease 2019 (COVID-19) infection has been known and the experts have started working on the enzyme ACE-2 for the management and treatment of this pandemic disease. The binding of spike (S) protein of SARS-CoV-2 to these receptors is the most important step and plays a key role in viral replication, thus this enzyme is becoming the doorway for the entry and spread in the human body causing asymptomatic pneumonia and severe of which is leading to death. As no specific method to prevent and treat this disease is available, the use of ACE-2 as a targeting ligand with COVID-19 virus spike protein could be helpful in the proper management of SARS-CoV-2 pneumonia.

Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

Accumulating data has shown a contribution of the renin‐angiotensin system in COVID‐19 pathogenesis. The role of angiotensin‐converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID‐19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case‐control study and assessed the impact of ACE I/D genotype in COVID‐19 disease prevalence and severity. In 81 COVID‐19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID‐19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0‐fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266–2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051–1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID‐19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID‐19 patients compared to healthy individuals and set the grounds for large‐scale studies assessing ACE genotype‐based optimized therapies with ACE inhibitors and angiotensin receptor blockers.

Infection of Human Cells by SARS-CoV-2 and Molecular Overview of Gastrointestinal, Neurological, and Hepatic Problems in COVID-19 Patients.

The gastrointestinal tract is the body’s largest interface between the host and the external environment. People infected with SARS-CoV-2 are at higher risk of microbiome alterations and severe diseases. Recent evidence has suggested that the pathophysiological and molecular mechanisms associated with gastrointestinal complicity in SARS-CoV-2 infection could be explained by the role of angiotensin-converting enzyme-2 (ACE2) cell receptors. These receptors are overexpressed in the gut lining, leading to a high intestinal permeability to foreign pathogens. It is believed that SARS-CoV-2 has a lesser likelihood of causing liver infection because of the diminished expression of ACE2 in liver cells. Interestingly, an interconnection between the lungs, brain, and gastrointestinal tract during severe COVID-19 has been mentioned. We hope that this review on the molecular mechanisms related to the gastrointestinal disorders as well as neurological and hepatic manifestations experienced by COVID-19 patients will help scientists to find a convenient solution for this and other pandemic events.

Malaria, COVID-19 and angiotensin-converting enzyme 2: what does the available population data say?

The etiopathogenesis of COVID-19 and its differential geographic spread suggest some populations are apparently 'less affected' through many host-related factors that involve angiotensin-converting enzyme 2 (ACE2) protein, which is also the entry receptor for SARS-CoV-2. The role of ACE2 has been well studied in COVID-19 but not in the context of malaria and COVID-19. We have previously suggested how malaria might intersect with COVID-19 through ACE2 mutation and here we evaluate the currently available data that could provide a link between the two diseases. Based on the existing global and Indian data on malaria, COVID-19 and the suggested ACE2 mutation, the association could not be examined robustly, neither accepting nor refuting the suggested hypothesis. We strongly recommend targeted evaluation of this hypothesis through carefully designed robust molecular epidemiological studies.

COVID-19 in Children: Do They Have a Lower Risk of Severe Infection Than Adults?

: The novel coronavirus disease 2019 (COVID-19), which was first identified in Wuhan, China, in late 2019, has now spread around the world. It significantly affects the lower respiratory tract, and pneumonia is always present in patients with the severe form of the disease. Many studies have shown that the severity of COVID-19 is lower in pediatric populations. It is important to determine why infants and young children are not severely affected by COVID-19. By increasing our awareness of this disease, we can prioritize our limited health resources. Several theories have been proposed to explain such significant differences between the pediatric and adult populations with COVID-19. Some of them are: (1) the role of angiotensin-converting enzyme 2 (ACE2); (2) cross-immunity with other severe acute respiratory syndrome (SARS)-like viruses; (3) obtunded systemic inflammatory response in children; (4) more efficient T cells in them; (5) interactions of SARS-Coronavirus-2 (SARS-CoV-2) with other viruses in the mucosa of the lungs and airways; and (6) a hypothesis that COVID-19 proteins onslaught the heme on the β-1 chain of hemoglobin. The important thing to keep in mind is that the asymptomatic and mildly symptomatic pediatrics are crucial in the spread of COVID-19.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Abstract P160: Deficiency Of Angiotensin-converting Enzyme In Renal Proximal Convoluted Tubules Does Not Attenuate Atherosclerosis In Mice

Objective: Angiotensin-converting enzyme (ACE) is the enzyme to generate Angiotensin II (AngII), an important contributor to atherosclerosis. ACE is present in all 3 segments (S1, S2, and S3) of proximal tubular cells (PTCs), and AngII concentrations are higher in kidney than in plasma. The purpose of this study was to determine whether ACE in PTCs contributes to atherosclerosis in mice. Approach and Results: Female ACE floxed mice and male Ndrg1-Cre ERT2 +/- transgenic mice were bred to generate ACE f/f x Ndrg1-Cre ERT2 -/- (PTC-ACE +/+ ) and ACE f/f x Ndrg1-Cre ERT2 +/- (PTC-ACE -/- ) littermates. Male PTC-ACE +/+ (n=7) and PTC-ACE -/- (n=10) littermates in an LDL receptor -/- background were used for atherosclerosis study. After Cre genotyping using tail DNA, mice (both Cre ERT2 -/- and Cre ERT2 +/- ) were injected with 150 mg/kg/day of tamoxifen for 5 consecutive days at the age of 4-6 weeks. Two weeks after the last injection of tamoxifen, mice were fed a Western diet (Envigo, Diet #TD.88137) for 12 weeks to induce hypercholesterolemia. Blood pressure was measured using a tail-cuff system. No difference of blood pressure was detected between the two genotypes (PTC-ACE +/+ vs. PTC-ACE -/- : 126 ± 4 vs. 125 ± 3 mmHg; P = 0.763). All study mice were hypercholesterolemic, but plasma cholesterol concentrations were not different between the two genotypes (PTC-ACE +/+ vs. PTC-ACE -/- : 1376 ± 119 vs. 1543 ± 93 mg/dl; P = 0.28). PTC-specific deletion of ACE was confirmed after termination using immunostaining of ACE. In mice with Ndrg1-Cre ERT2 transgene, immunostaining of ACE in kidney section showed an absence of ACE in S1 and S2 of PTCs, but ACE protein in S3 remained. Deletion of ACE in S1 and S2 of PTCs did not change hypercholesterolemia-induced atherosclerosis in the ascending and aortic arch regions (PTC-ACE +/+ vs. PTC-ACE -/- : 9.6 ± 0.9% vs. 7.0 ± 1.9%; P = 0.13 by Mann-Whitney Rank Sum Test), as measured using an en face method. Conclusion: ACE deficiency in S1 and S2 of renal proximal tubular cells had no effect on atherosclerosis in hypercholesterolemic mice. Since ACE is more abundant in S3 than in S1 and S2 of PTCs, it would be important to determine the role of ACE in the S3 segment.

The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression Levels in Patients with Comorbidities on COVID-19 Severity: A Comprehensive Review.

Angiotensin-Converting Enzyme 2 (ACE2) has been proved to be the main host cell receptor for the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. The SARS-CoV-2 spike (S) protein binds to ACE2 to initiate the process of replication. This enzyme is widely present in human organ tissues, such as the heart and lung. The pathophysiology of ACE2 in SARS-CoV-2 infection is complex and may be associated with several factors and conditions that are more severe in COVID-19 patients, such as age, male gender, and comorbidities, namely, cardiovascular diseases, chronic respiratory diseases, obesity, and diabetes. Here we present a comprehensive review that aims to correlate the levels of expression of the ACE2 in patients with comorbidities and with a poor outcome in COVID-19 disease. Significantly higher levels of expression of ACE2 were observed in myocardial and lung tissues in heart failure and COPD patients, respectively. An age-dependent increase in SARS2-CoV-2 receptors in the respiratory epithelium may be also responsible for the increased severity of COVID-19 lung disease in elderly people. Although the role of ACE2 is highlighted regarding the damage that can arise upon the SARS-CoV-2 invasion, there was no association observed between renin-angiotensin-aldosterone system (RAAS) inhibitors and the severity of COVID-19.

Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin–Angiotensin–Aldosterone System (RAAS) and Kinin–Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.

Decipering the Molecular Mechanism of ACE2 Regulating A549 Cells.

Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.

Renin Angiotensin System Inhibition as treatment for Covid-19?

Renin Angiotensin System Inhibition as treatment for Covid-19?