Role Of Angiotensin-converting Enzyme Research Articles

COVID-19, Renin-Angiotensin System and Endothelial Dysfunction.

The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1–9 and Ang 1–7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.

Coronavirus Disease 2019 and Hypertension: The Role of Angiotensin-Converting Enzyme 2 and the Renin-Angiotensin System.

Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19, into host cells. Because RAS inhibitors have been suggested to increase ACE2 expression, health-care providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.

COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease

SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. Chronic pulmonary disease is underrepresented in the group with severe COVID-19. A commonality of aberrant renin angiotensin system (RAS) is suggested in the at-risk group. The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis.We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation. Additionally, there is a profound loss of the “protective” angiotensin (1–7), a vasodilator with anti-inflammatory, anti-thrombotic, antiproliferative, antifibrotic, anti-arrhythmic, and antioxidant activity. Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than “cytokine storm”. Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices.

COVID-19 and renin-angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) - Is there any scientific evidence for controversy?

Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.

June 2020 at a glance: focus on COVID-19, quality of life and comorbidities.

Patients with heart failure (HF) are at increased risk of infections, and infections may precipitate acute HF and be a major cause of morbidity and mortality.1, 2 These threatening relationships have been magnified by the recent coronavirus disease 2019 (COVID-19) pandemic. Management of HF patients with concomitant COVID-19 is a major challenge. To support HF specialists in this difficult task, the Chinese HF Association and National HF Committee and the HF Association of the European Society of Cardiology developed a joint position paper summarizing current literature and clinical experience to give all possible guidance for the management of patients with HF and COVID-19 in clinical practice.3 The peculiar aspects of COVID-19 were integrated with the most recent findings for HF treatment.3, 4 The renin–angiotensin system has a pivotal role in HF.5 The angiotensin converting enzyme 2 (ACE2) is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was hypothesized that it may be upregulated by angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) treatment. Tomasoni et al.6 reviewed the relationships between HF and COVID-19 and the role of ACE2 and ACEi/ARB treatment in the pathophysiology and outcome of COVID-19 showing the lack of data supporting an untoward role of these drugs in COVID-19. Consistently, Bean et al.7 analysed a large series of HF patients hospitalized for COVID-19 and found a 37% reduction in the risk of death or need for transfer to a critical care unit in patients on ACEi or ARB, thus supporting the recommendation to continue treatment with these drugs also during the COVID-19 pandemic. The COVID-19 pandemic was associated with a dramatic decrease in the number of hospital admissions for acute cardiac emergencies.8 Also admissions for acute HF decreased during the COVID-19 outbreak despite no differences in HF severity, patients' care and pharmacological management compared with before.9 Telemonitoring therefore appears as the best solution for patients' follow-up.3 To date, patients' selection for telemonitoring has been difficult and use of natriuretic peptides was proposed.10 Galinier et al.11 report the results of a randomized, multicentre, open-label study investigating the role of telemedicine, compared to standard care, in preventing death or HF hospitalization (primary endpoint). The advantage of telemonitoring vs. standard care was noted only in patients with New York Heart Association class III/IV and in those with high adherence to body weight measurements. Quality of life (QOL) has become a major endpoint for HF studies.12-14 Butler et al.15 evaluated the association between changes in QOL scores and clinical improvement perceived by the patient, defined as minimal clinically important difference (MCID), in patients with chronic HF and iron deficiency treated with intravenous iron or placebo. They found that QOL scores were consistent although lower than MCID changes, suggesting that even small changes in QOL scores are clinically significant. Reddy et al.16 investigated the association of QOL reported by patients with HF and preserved ejection fraction (HFpEF) and HF severity defined according to aerobic capacity, exercise capacity, volume of daily activity, functional class, resting echocardiography, and plasma natriuretic peptide levels. QOL was found to be poorest in young, obese and diabetic patients. Poorer QOL was associated with worse physical capacity and activity levels, but was not associated with N-terminal pro B-type natriuretic peptide or echocardiographic parameters. Cardiac and non-cardiac comorbidities are associated with poor outcomes in HF patients.17, 18 Nevertheless, Khan et al.19 found that only 51% of HF with reduced ejection fraction (HFrEF) trials and 27% of HFpEF trials reported baseline comorbidities. The most common reported comorbidities were hypertension (63%), ischaemic heart disease (44%), hyperlipidaemia (48%), diabetes (33%), chronic kidney disease (25%) and atrial fibrillation (25%). Patients' heterogeneity is large in acute HF.20, 21 Bhatt et al.22 stratified 6945 patients with acute HF according to the number of non-cardiac comorbidities. The highest rate of all-cause death or HF hospitalization was observed in patients with four or more comorbidities. The relative risk of the composite endpoint increased with the number of comorbidities at both 30 days and 6 months. Higher comorbidity burden was associated with higher costs of care and length of stay.

Reply to Siniorakis et al., "COVID-19 Interference with Renin-Angiotensin System in the Context of Heart Failure".

We thank Eftychios Siniorakis and colleagues for their thoughtful letter on how repurposing statins and angiotensin receptor blockers (ARBs) for coronavirus disease 2019 (COVID-19) treatment might affect patients with heart failure (1). Our understanding of the pathophysiology of COVID-19 disease has advanced rapidly in the past few months. The immunological dysregulation associated with the disease and the cardiovascular effects of infection (and especially the role of angiotensin converting enzyme 2 [ACE2]) have been comprehensively reviewed (2–7). Some patients who develop acute respiratory distress syndrome (ARDS) can be severely hypoxic and yet show relatively normal pulmonary compliance (8). Endothelial dysfunction and intense inflammation seem to be important contributors to their distress (9). In addition, pulmonary microvascular coagulopathy, sometimes associated with pulmonary or systemic embolization, has added a new dimension to clinical care (10–12). Many physicians have added anticoagulation to their treatments (13). Recently, van de Veerdonk and colleagues called attention to the contribution of the kallikrein-kinin system to COVID-19-induced ARDS (14, 15). Although much attention has been focused on the relationship between the renin-angiotensin system (RAS) and COVID-19 (5–7), there is considerable cross talk between the RAS and kallikrein-kinin systems (14–16). Experimentally, a reduction in ACE2 activity can impair inactivation of the B1 bradykinin receptor and this can be associated with an increase in inflammation-induced acute lung injury (17).

COVID-19 and the male susceptibility: the role of ACE2, TMPRSS2 and the androgen receptor

COVID-19 is the pandemic that hit the world starting December 2019. Recent studies and international statistics have shown an increased prevalence, morbidity as well as mortality of this disease in male patients compared to female patients. The aim of this brief communication is to describe the pathophysiology of this sex-discrepancy, based on the infectivity mechanism of the coronavirus including the Angiotensin-Converting Enzyme 2 (ACE2), the Type II transmembrane Serine Protease (TMPRSS2), and the androgen receptor. This could help understand the susceptibility of urological patients, especially those receiving androgen deprivation therapy for prostate cancer, and testosterone replacement therapy.

Diabetes and COVID-19: evidence, current status and unanswered research questions.

Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia.

SummaryThe lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.

At the heart of COVID-19.

Coronavirus disease(COVID-19) first presented in Wuhan, Hubei province, China in December 2019. Since then, it has rapidly spread across the world, and is now formally considered a pandemic. The disease does not discriminate but increasing age and the presence of comorbidities are associated with severe form of the disease and poor outcomes. Although the prevalence of COVID-19 in patients with cardiovascular disease is under-reported, there is evidence that pre-existing cardiac disease can render individuals vulnerable. It is thought that COVID-19 may have both a direct and indirect effect on the cardiovascular system; however, the primary mechanism of underlying cardiovascular involvement is still uncertain. Of particular interest is the role of angiotensin-converting enzyme 2, which is well known for its cardiovascular effects and is also considered to be important in the pathogenesis of COVID-19. With a range of different drug candidates being suggested, effective anti-virals and vaccines are an area of on-going research. While our knowledge of COVID-19 continues to rapidly expand, this review highlights recent advances in our understanding of the interaction between COVID-19 and the cardiovascular system.

SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications

The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world – this is the most recent and alarming update. COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure. Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death. To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease. Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body. The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2). Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects. Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD. This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients. In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization. We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.

Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues

BackgroundSince its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.MethodsWe compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson’s correlation test.ResultsACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.ConclusionsOur data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease.

Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin–angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.

Aerobic Exercise Training Prevents Obesity and Insulin Resistance Independent of Changes in the Skeletal Muscle ACE2/Ang 1‐7/Mas Axis.

Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). Improvements in the oxidative capacity of skeletal muscle can mediate the protective effect of AET. Considering the role of angiotensin converting enzyme 2 (ACE2)/angiotensin 1‐7 (Ang 1‐7)/receptor Mas axis activation in reducing cardiometabolic diseases, the present study aimed to evaluate if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1‐7)/Mas axis in the skeletal muscle. Adult male C57BL6/J mice were assigned into groups (n=10/group): chow‐fed controls (C), chow‐fed trained (T), cafeteria diet (CAF), and cafeteria diet and trained (CAFT). AET was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from School of Arts, Science and Humanities, University of Sao Paulo, Brazil (#001/2016). The CAF group presented higher body weight gain and adiposity, glucose intolerance, IR and increased lipid deposition in the liver while AET prevented such damages in the CAFT group. Food consumption did not change among the groups. During the maximal physical exertion test, the T group increased VO2máx and both T and CAFT groups showed higher maximal speed, higher speed on the VO2máx and lower relative running cost compared to C and CAF groups. The enzymatic activity of citrate synthase and β‐hydroxyacyl‐CoA dehydrogenase (β‐HAD) in the soleus muscle increased in the T (352 ± 21.5 mmol/min/mg and 80.1 ± 6.6 mmol/min/mg) and CAFT (350 ± 22.4 mmol/min/mg and 87.9 ± 7.3 mmol/min/mg) groups compared to C (272.7 ± 9.5 mmol/min/mg and 62.7 ± 3.9 mmol/min/mg) and CAF (254.6 ± 15.7 mmol/min/mg and 46.7 ± 1.6 mmol/min/mg) groups. Protein expression of mitofusin 1, mitofusin 2 and dynamin related protein 1 (Drp1) did not change among groups. Also, no differences were observed in the ACE2 and Ang (1‐7) levels nor in the receptor Mas protein expression. In conclusion, the AET prevented the increase in body weight, adiposity and IR induced by cafeteria diet, improved the aerobic capacity and promoted the increase in oxidative enzymes activity in the soleus muscle. However, the adaptations induced by AET were not associated with changes in the ACE2/Ang (1‐7)/Mas axis in the skeletal muscle.Support or Funding InformationSão Paulo Research Foundation (FAPESP #2015/04948‐4; #2016/23783‐9; #2016/20659‐5).

Study the biochemical and molecular role of angiotensin converting enzyme in migraine and non-migraine headache

Study the biochemical and molecular role of angiotensin converting enzyme in migraine and non-migraine headache

Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?

Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

ACE2 Attenuates Epithelial-Mesenchymal Transition in MLE-12 Cells Induced by Silica.

PurposeThe role of angiotensin-converting enzyme 2 (ACE2) in silicosis remains unknown, although previous studies have suggested that ACE2 may be beneficial. We, therefore, investigated the effect of ACE2 on silicosis, particularly with regard to its role in regulating the epithelial-mesenchymal transition (EMT) induced by silica, with the aim to uncover a new potential target for the treatment of pulmonary fibrosis.Materials and MethodsWe employed wild-type mice treated with diminazene aceturate (DIZE, an ACE2 activator, 15 mg/kg/day for 4 weeks), hACE2-transgenic mice (overexpress the ACE2 gene), and the mouse lung type II epithelial cell line treated with DIZE (10−7 M for 48 h) or angiotensin-(1–7) [Ang-(1–7)] (10−4 M for 48 h), following induced fibrotic responses to determine the protective potential of ACE2. Silicosis models were established by orotracheal instillation of SiO2 (2.5 mg/mouse). Immunostaining was used to determine α-smooth muscle actin (α-SMA) expression. The activities of angiotensin-converting enzyme (ACE) and ACE2 and the levels of angiotensin II (Ang II) and Ang-(1-7) were detected by enzyme-linked immunosorbent assay. The mRNA expression of ACE and ACE2, and protein expression of the renin-angiotensin system (RAS) components and EMT indicators were studied by qRT-PCR and Western blot, respectively.ResultsDIZE treatment and overexpression of ACE2 markedly inhibited the formation of silica-induced lung fibrosis and increased the level of E-cadherin, with concomitant downregulation of pro-collagen, vimentin, and α-SMA via RAS signaling. Furthermore, DIZE and Ang-(1–7) attenuated the EMT and collagen deposition induced by silica in MLE-12 cells. Moreover, these effects were abrogated by MLN-4760 (a specific ACE2 inhibitor) and A779 (a specific Mas receptor blocker).ConclusionThe overexpression of ACE2 and treatment with DIZE can ameliorate EMT in silicotic mice via activation of the ACE2-Ang-(1–7)-Mas receptor axis, and these changes are accompanied by suppression of the ACE–Ang II–AT1 receptor axis.

COVID-19, diabetes mellitus and ACE2: The conundrum

COVID-19, diabetes mellitus and ACE2: The conundrum

Serum Level of the Angiotensin-Converting Enzyme in Patients with Idiopathic Acute Optic Neuritis: A Case-Control Study.

Purpose To evaluate the serum level of angiotensin-converting enzyme (ACE) as an important component of the renin-angiotensin system (RAS) in optic neuritis (ON) compared to the healthy control group in the context investigating the possible role of ACE in ON pathogenesis. Methods This case-control study was conducted on patients with ON and healthy controls. Serum ACE levels were assessed and compared between the two groups by using commercially available kits by ELISA for ACE. Results Sixty-five ON patients (75.4% female, mean age 29.70 ± 8.30 years) and 65 controls (75.4% female, mean age 29.66 ± 8.36 years) were enrolled. The median serum ACE levels were 33.5 U/L (range: 25–540) and 26 U/L (range: 22.3–72) for the ON patients and controls, respectively. Serum ACE levels were significantly higher in the patients than in the control group (P < 0.001). High level of serum ACE (defined as a serum ACE >65 U/L) was present in 9 (13.8%) patients with ON and 2 (3.1%) controls. Conclusion Our results indicated that the serum level of ACE appeared to be significantly higher in acute ON than in normal controls.