Role Of Angiotensin-converting Enzyme Research Articles

Association of Angiotensin Converting Enzyme Phenotypes and Polymorphisms with Clinical Outcomes in SARS-CoV2 Patients with Hypertension in an Urban Emergency Department.

The role of Angiotensin-converting enzyme (ACE and ACE2) phenotypes and polymorphisms in modulating severe acute respiratory syndrome coronavirus (SARS-- CoV2) infection in hypertensive patients remains unclear. Our objective was to determine the distribution of ACE and ACE2 receptor phenotypes by patient demographics and correlate ACE and ACE2 levels of activity with SARS-CoV-2 outcomes. Hypertensive patients treated for SARS-CoV-2 at an urban emergency department (ED) were prospectively enrolled in a cohort study between August 2020 and April 2021. Blood samples were collected during ED visits or hospitalization. Outcome measures including hospitalization, intensive care unit (ICU) admission, and 30-day mortality were obtained from electronic health records. Multivariable logistic regression was used. Of the 150 patients enrolled, 60% were Black, 32% Hispanic/Latinx, 4% Non-Hispanic Whites, and 4% others. The mean age was 59 (+/-14) years. The rate of hospitalization was high (86%) and Hispanic/Latinx had a higher likelihood of ICU admission. Patients harboring the rs2285666 genotype TT, AA, and GC alleles were more likely to be admitted to ICU, and those with TT and AA had higher mortality. The ACE level was a significant predictor of hospitalization with a protective effect in both unadjusted and adjusted results. Hispanics/Latinx had a four times higher likelihood of ICU admission compared to all others, and age was significantly associated with 30-day mortality. Our results show that even after adjusting for age, race, and sex, ACE levels remained a predictor of hospitalization. ACE/ACE2 phenotypes and genotypes potentially play an important role in disease progression in SARS-CoV-2 patients.

The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19.

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system. SARS-CoV-2 enters host cells by binding to ACE2, which may directly or indirectly affect the nervous system, leading to a range of neurological symptoms. This review aims to explore the function of ACE2 in the nervous system as well as its potential impact and therapeutic potential in various neurological diseases, providing a new perspective for the treatment of neurological disorders.

Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome and disease severity in adult patients: A prospective cohort study in a tertiary hospital, Indonesia.

Coronavirus disease 2019 (COVID-19) has led to a significant number of infections and deaths worldwide, yet its pathogenesis and severity remain incompletely understood. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), play crucial roles as receptors and molecules responsible for the virus's entry into host cells, initiating the infection process. Their polymorphisms have been extensively studied in relation to COVID-19 severity. The aim of this study was to examine the association of ACE2 (rs2074192) and TMPRSS2 (rs12329760) polymorphisms with COVID-19 outcome and severity. A prospective cohort study was conducted in 2022 at Haji Adam Malik Hospital, Medan, Indonesia. We randomly recruited hospitalized adult patients with COVID-19, confirmed by real-time polymerase chain reaction (RT-PCR). The baseline demographic data, disease severity, underlying disease, comorbidities, and COVID-19 vaccination status were collected. The single-nucleotide polymorphism (SNP) was assessed using TaqMan SNP genotyping assay, and the levels of TMPRSS2 and ACE2 proteins were measured using enzyme-linked immunosorbent assay (ELISA). A total of 151 COVID-19 patients were recruited and there were significant associations between age and severity with mortality outcomes. The age, kidney and lung diseases, and vaccination status were associated with severity levels. The results showed the CC genotype of ACE2 had the highest proportion, followed by TT and CT genotypes among patients, while CT was the most prevalent genotype, followed by CC and TT for TMPRSS2. This study did not find a significant association between ACE2 and TMPRSS2 genetic variants with disease severity and outcome but highlighted a specific association of TMPRSS2 SNP with mortality within the group. In addition, ACE2 concentration was significant different between mild-moderate and severe-critical COVID-19 groups (p=0.033).

ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway.

Neuroinflammation and oxidative stress contribute to the progression of sepsis-associated encephalopathy (SAE). Angiotensin-converting enzyme 2 (ACE2) is considered to be a neuroprotective factor due to its anti-inflammatory and antioxidant properties. However, the role of ACE2 on myeloid cells in regulating SAE and the underlying mechanism warrants further exploration. SAE was induced in ACE2 transgenic (TG), knockout (KO), and bone marrow (BM) chimeric mice by cecal ligation and puncture (CLP). The expression levels of apoptosis-, oxidation- and neuroinflammation-associated mediators and morphological changes were monitored by quantitative real-time PCR analyses and histological examinations in the cortex of septic mice. The contents of angiotensin (Ang) II and Ang-(1-7) along with the activity of ACE2 were examined with commercial kits. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2 was detected by immunoblotting analysis. Our results indicated that the expression of cortical ACE2 was significantly reduced in the early phase of CLP-induced sepsis. Moreover, ACE2 overexpression in TG mice conferred neuroprotection against sepsis, as evidenced by alleviated neuronal apoptosis, oxidative stress, and proinflammatory M1-like microglial polarization, accompanied by upregulation of the Ang-(1-7), Nrf2, and Sestrin2 protein levels. Conversely, ACE2 deficiency in KO mice exacerbated SAE. The neuroprotective effects of ACE2 were further confirmed in wild-type mice transplanted with ACE2-TG and KO BM cells. Therefore, our data suggest that myeloid ACE2 exerts a protective role in the pathogenesis of SAE, potentially by activating Ang-(1-7)-Nrf2/sestrin2 signaling pathway, and highlight that upregulating ACE2 expression and activity may represent a promising approach for the treatment of SAE in patients with sepsis.

The Role of Angiotensin-Converting Enzyme (ACE) Polymorphisms in the Risk of Development and Treatment of Diabetic Nephropathy.

Angiotensin-converting enzyme (ACE) is responsible for the production of angiotensin II, and increased production of angiotensin II is observed in diabetes. What is more, ACE polymorphisms may play a role in the development of diabetic nephropathy. The aim of this study was to assess the role of selected ACE polymorphisms (rs4343 and rs4646994) in the risk of development of diabetic nephropathy and in the likelihood of renal replacement therapy. ACE polymorphisms were analyzed in a group of 225 patients who were divided into three subgroups. The rs4343 polymorphism was determined using the PCR-RFLP, and the rs4646994 polymorphism was determined using the PCR. Molecular docking between domains of ACE and its ligands was performed by using AutoDock Vina. The G/G genotype of rs4343 polymorphism is associated with increased odds of developing diabetic nephropathy. The G allele is also associated with a higher risk of this disease. Similar results were obtained in patients who had already had a kidney transplant as a result of diabetic nephropathy. The presence of G/G and G/A genotypes, and the G allele increases the likelihood of developing diabetic nephropathy. This may also be a risk factor for renal replacement therapy.

The roles of angiotensin-converting enzyme 2 inhibitor, melatonin and its agonist on angiotensin II reactivity in intact and denuded rat aortic rings

Background The pineal product melatonin (MEL) modulates blood vessels through G protein-coupled receptors (GPCRs) called melatonin type 1 receptor (MT1R) and melatonin type 2 receptor (MT2R), in that order. The renin-angiotensin system (RAS), which breaks down angiotensin II (Ang II) to create Ang 1–7, is thought to be mostly controlled by angiotensin-converting enzyme-2 (ACE2). Aim The current work examines the involvement of ACE2 inhibitor, MEL, and ramelteon (RAM) in the vascular response to Ang II activities in the endothelial denuded (E-) and intact (E+) rat isolated thoracic aortic rings. Method The isometric tension was measured to evaluate the vascular Ang II contractility using dose response curve (DRC). Results MEL and RAM caused a rightward shift of Ang II in endothelium E + and endothelium E- aorta. Conclusion According to the current study, the distribution of MEL receptors and the endothelium’s condition are related to the vasomodulatory effect of MEL and ACE2 on Ang II attenuation. These physiological interactions can control vascular tone and increase Ang II reactivity denude endothelial layaer.

ACE2 activation alleviates sepsis-induced cardiomyopathy by promoting MasR-Sirt1-mediated mitochondrial biogenesis

Sepsis-induced cardiomyopathy (SIC), caused by a dysregulated host response to infection, is a major contributor to high mortality. Angiotensin-converting enzyme 2 (ACE2), a crucial component of the renin-angiotensin system (RAS), has protective effects against several cardiovascular diseases, such as myocardial infarction and heart failure. However, the role of ACE2 in the pathogenesis of SIC and underlying mechanisms remain unknown. The present study was designed to examine the effects of ACE2 activation or inhibition on SIC in C57BL/6 mice. The ACE2 activator diminazene aceturate (DIZE) and ACE2 inhibitor MLN-4760 were applied for treatment. Myocardial function, inflammatory response, oxidative stress, apoptosis and mitochondrial biogenesis were investigated. Major assays were echocardiography, H&E staining, immunofluorescence staining, DHE staining, TUNEL staining, Western blot, qPCR analysis, ELISA and corresponding kits. We confirmed that ACE2 was markedly downregulated in septic heart tissues. Pharmacological activation of ACE2 by DIZE ameliorated cecal ligation puncture (CLP)-induced mortality, cardiac dysfunction, inflammatory response, oxidative stress and the cardiomyocyte apoptosis by promoting MasR-Sirt1-mediated mitochondrial biogenesis. In contrast, SIC was aggravated via inhibiting MasR-Sirt1-mediated mitochondrial biogenesis by the use of ACE2 inhibitor MLN-4760. Consequently, activation of ACE2 may protect against SIC by promoting MasR-Sirt1-mediated mitochondrial biogenesis.

Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome.

Long COVID-19 syndrome is present in 5-10% of patients infected with SARS-CoV-2, and there is still little information on the predisposing factors that lead to its development. The purpose of the study was to evaluate the predictive factors in early symptoms, clinical features and the role of Angiotensin-Converting Enzyme-2 (ACE-2) c.513-1451G>A (rs2106806) and c.15643279T>C (rs6629110) polymorphisms in the susceptibility to developing Long COVID-19 syndrome subsequent to COVID-19 infectionA total of 29 patients who suffered COVID-19 were recruited in a descriptive longitudinal study of two groups: Long COVID-19 (n = 16) and non-Long COVID-19 (n = 13). Early symptoms and clinical features during COVID-19 were classified by a medical service. ACE-2 polymorphisms were genotyped by using a Single Nucleotide Primer Extension (SNPE). Of the early symptoms, fatigue, myalgia and headache showed a high risk of increasing Long COVID-19 susceptibility. Clinical features such as emergency care, SARS-CoV-2 reinfection, previous diseases, respiratory disease and brain fog also had a high risk of increasing Long COVID-19 susceptibility. The A allele in the rs2106806 variant was associated with an odds ratio (OR) of 4.214 (95% CI 2.521-8.853; p < 0.001), and the T allele in the rs6629110 variant was associated with an OR of 3.754 (95% CI 1.785-6.105; p = 0.002) of increasing Long COVID-19 susceptibility. This study shows the risk of ACE-2 polymorphisms, different early symptoms and clinical features during SARS-CoV-2 infection in susceptibility to Long COVID-19.

SARS-CoV-2 spike protein induces endothelial inflammation via ACE2 independently of viral replication

COVID-19, caused by SARS-CoV-2, is a respiratory disease associated with inflammation and endotheliitis. Mechanisms underling inflammatory processes are unclear, but angiotensin converting enzyme 2 (ACE2), the receptor which binds the spike protein of SARS-CoV-2 may be important. Here we investigated whether spike protein binding to ACE2 induces inflammation in endothelial cells and determined the role of ACE2 in this process. Human endothelial cells were exposed to SARS-CoV-2 spike protein, S1 subunit (rS1p) and pro-inflammatory signaling and inflammatory mediators assessed. ACE2 was modulated pharmacologically and by siRNA. Endothelial cells were also exposed to SARS-CoV-2. rSP1 increased production of IL-6, MCP-1, ICAM-1 and PAI-1, and induced NFkB activation via ACE2 in endothelial cells. rS1p increased microparticle formation, a functional marker of endothelial injury. ACE2 interacting proteins involved in inflammation and RNA biology were identified in rS1p-treated cells. Neither ACE2 expression nor ACE2 enzymatic function were affected by rSP1. Endothelial cells exposed to SARS-CoV-2 virus did not exhibit viral replication. We demonstrate that rSP1 induces endothelial inflammation via ACE2 through processes that are independent of ACE2 enzymatic activity and viral replication. We define a novel role for ACE2 in COVID-19- associated endotheliitis.

An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)—the cellular receptor of SARS-CoV-2—into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.

The effects of enhancing angiotensin converting enzyme in myelomonocytes on ameliorating Alzheimer's-related disease and preserving cognition.

This review examines the role of angiotensin-converting enzyme (ACE) in the context of Alzheimer's disease (AD) and its potential therapeutic value. ACE is known to degrade the neurotoxic 42-residue long alloform of amyloid β-protein (Aβ42), a peptide strongly associated with AD. Previous studies in mice, demonstrated that targeted overexpression of ACE in CD115+ myelomonocytic cells (ACE10 models) improved their immune responses to effectively reduce viral and bacterial infection, tumor growth, and atherosclerotic plaque. We further demonstrated that introducing ACE10 myelomonocytes (microglia and peripheral monocytes) into the double transgenic APPSWE/PS1ΔE9 murine model of AD (AD+ mice), diminished neuropathology and enhanced the cognitive functions. These beneficial effects were dependent on ACE catalytic activity and vanished when ACE was pharmacologically blocked. Moreover, we revealed that the therapeutic effects in AD+ mice can be achieved by enhancing ACE expression in bone marrow (BM)-derived CD115+ monocytes alone, without targeting central nervous system (CNS) resident microglia. Following blood enrichment with CD115+ ACE10-monocytes versus wild-type (WT) monocytes, AD+ mice had reduced cerebral vascular and parenchymal Aβ burden, limited microgliosis and astrogliosis, as well as improved synaptic and cognitive preservation. CD115+ ACE10-versus WT-monocyte-derived macrophages (Mo/MΦ) were recruited in higher numbers to the brains of AD+ mice, homing to Aβ plaque lesions and exhibiting a highly Aβ-phagocytic and anti-inflammatory phenotype (reduced TNFα/iNOS and increased MMP-9/IGF-1). Moreover, BM-derived ACE10-Mo/MΦ cultures had enhanced capability to phagocytose Aβ42 fibrils, prion-rod-like, and soluble oligomeric forms that was associated with elongated cell morphology and expression of surface scavenger receptors (i.e., CD36, Scara-1). This review explores the emerging evidence behind the role of ACE in AD, the neuroprotective properties of monocytes overexpressing ACE and the therapeutic potential for exploiting this natural mechanism for ameliorating AD pathogenesis.

P-040 The Role of ACE2 and DNA fragmentation index on covid-19 post infected, healthy and infertile men

Abstract Study question to investigate the relationship between ACE2 and DNA fragmentation index and their impact on men’s reproductive system in covid-19 post-infected patients. Summary answer the drastic effect of covid-19 on the male reproductive system might be due to elevated DFI and ACE2 levels. What is known already In the last two years, many studies had been devoted to uncovering the depraved impact of covid-19 by measuring ACE2 concentrations or sperm DNA fragmentation but no study was applied to measure both parameters, this study performed on both parameters to figure out the role of angiotensin-converting enzyme (ACE2) with seminal fluid parameters and DNA fragmentation index in covid-19 post infected men and infertile patient in comparison to healthy fertile men. Study design, size, duration This prospective cohort study was conducted from November 2021 to June 2022. one hundred and nine men who participated in this study. Participants/materials, setting, methods The participants were divided into four groups: post-infected men with Covid-19 who recovered from Covid-19 infection with a recovery interval of no more than three months from the time of symptoms onset and all were fertile married men, healthy fertile men who haven't been infected with Covid-19 in the last three months obtain normal seminal fluid parameters as control, The third group is composed of oligospermia, while the fourth group is constituted of azoospermia volunteers Main results and the role of chance In this study, the result showed that the seminal fluid parameters for post-infected men with covid-19; were demotion in sperm concentration, total count, motility, and morphology with a p-value &amp;lt; 0.001 when compared with healthy men. DNA fragmentation in post-infected men was 4 times higher than in non-infected and it was found that post-infected men had 10 times more ACE2 concentrations in comparison with healthy men. The study showed that in oligospermia and azoospermia volunteers own a high ACE2 level compared to healthy volunteers and that the oligospermia subjects have a significantly high sperm DNA fragmentation index. In conclusion, the drastic effect of covid-19 on the male reproductive system might be due to elevated DNA fragmentation and ACE2 levels, and there is a statistically significant positive correlation between the DNA fragmentation index and ACE2 levels. Limitations, reasons for caution number of post-infected men with covid-19 Wider implications of the findings 1- A positive relationship exists between DNA fragmentation index percentage (DFI) and angiotensin-converting enzyme level (ACE 2). 2- Covid-19 infection alters sperm parameters such as concentrations, total sperm count, motility, and morphology. 3- The percentage of DNA fragmentation rose significantly after covid-19 infection. Trial registration number self funding

COVID-19 and the cardiovascular system: a study of pathophysiology and interpopulation variability.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans can lead to various degrees of tissue and organ damage, of which cardiovascular system diseases are one of the main manifestations, such as myocarditis, myocardial infarction, and arrhythmia, which threaten the infected population worldwide. These diseases threaten the cardiovascular health of infected populations worldwide. Although the prevalence of coronavirus disease 2019 (COVID-19) has slightly improved with virus mutation and population vaccination, chronic infection, post-infection sequelae, and post-infection severe disease patients still exist, and it is still relevant to study the mechanisms linking COVID-19 to cardiovascular disease (CVD). This article introduces the pathophysiological mechanism of COVID-19-mediated cardiovascular disease and analyzes the mechanism and recent progress of the interaction between SARS-CoV-2 and the cardiovascular system from the roles of angiotensin-converting enzyme 2 (ACE2), cellular and molecular mechanisms, endothelial dysfunction, insulin resistance, iron homeostasis imbalance, and psychosocial factors, respectively. We also discussed the differences and mechanisms involved in cardiovascular system diseases combined with neocoronavirus infection in different populations and provided a theoretical basis for better disease prevention and management.

Pain in COVID-19 and features of pathogenetic molecular mechanisms

Although it has been almost three years since the World Health Organization (WHO) declared a pandemic, COVID-19 is still an unsolved problem, thereby attracting great scientific interest. The disease has a heterogeneous clinical picture with multiple manifestations from different organs and systems. Currently, COVID-19 is perceived as a polysyndromic inflammatory disease involving not only the respiratory system, but also the musculoskeletal system, the cardiovascular system, the skin, the excretory and the nervous system, and is accompanied by a number of hematological, gastrohepatoenterological and endocrine disorders. Various pain phenomena also appear in the clinical presentation of the disease, often as a single manifestation or in combination with symptoms from different organs and systems. The pathogenesis of pain is complex and there is still no consensus on the exact driving mechanisms. Several different signaling pathways play an important role in the generation of pain impulses and perception. They are different for different types of pain. At this stage, the role of angiotensin-converting enzyme 2 (ACE), the renin-angiotensin system (RAC), angiotensin 2 receptors (AT2R), direct neuronal invasion of the virus, the involvement of pro-inflammatory cytokines, hypoxia, the involvement of macrophages, is discussed. as well as the role of overactivity of the immune system, causing the so-called "cytokine storm". Pain is the result of complex biochemical processes influenced to varying degrees by biological, physiological and social factors. Our knowledge at this stage remains scarce and is the subject of many studies on the key pathogenic mechanisms. Therefore, the purpose of this review is to describe the known mechanisms for the occurrence and persistence of pain in patients with COVID-19, as well as to classify the pain phenomena and present its most common localizations. The diagnosis and treatment of COVID-19 and associated pain should be carried out by a multidisciplinary team of specialists, given the heterogeneous clinical presentation of the disease.

Macrophages and γδ T cells interplay during SARS-CoV-2 variants infection.

The emergence of several SARS-CoV-2 variants during the COVID pandemic has revealed the impact of variant diversity on viral infectivity and host immune responses. While antibodies and CD8 T cells are essential to clear viral infection, the protective role of innate immunity including macrophages has been recognized. The aims of our study were to compare the infectivity of different SARS-CoV-2 variants in monocyte-derived macrophages (MDM) and to assess their activation profiles and the role of ACE2 (Angiotensin-converting enzyme 2), the main SARS-CoV-2 receptor. We also studied the ability of macrophages infected to affect other immune cells such as γδ2 T cells, another partner of innate immune response to viral infections. We showed that the SARS-CoV-2 variants α-B.1.1.7 (United Kingdom), β-B.1.351 (South Africa), γ-P.1 (Brazil), δ-B.1.617 (India) and B.1.1.529 (Omicron), infected MDM without replication, the γ-Brazil variant exhibiting increased infectivity for MDM. No clear polarization profile of SARS-CoV-2 variants-infected MDM was observed. The β-B.1.351 (South Africa) variant induced macrophage activation while B.1.1.529 (Omicron) was rather inhibitory. We observed that SARS-CoV-2 variants modulated ACE2 expression in MDM. In particular, the β-B.1.351 (South Africa) variant induced a higher expression of ACE2, related to MDM activation. Finally, all variants were able to activate γδ2 cells among which γ-P.1 (Brazil) and β-B.1.351 (South Africa) variants were the most efficient. Our data show that SARS-CoV-2 variants can infect MDM and modulate their activation, which was correlated with the ACE2 expression. They also affect γδ2 T cell activation. The macrophage response to SARS-CoV-2 variants was stereotypical.

Single nucleotide polymorphism in Angiotensin-converting enzyme-2 gene as a risk for COVID-19 among Iraqi people

Angiotensin-converting enzyme-2 (ACE-2) is an essential element in the renin-angiotensin RAS system and plays a key role in coronavirus entrance to the human body and attachment to the cell. Variation in ACE-2 may increase the capability of coronavirus to binding with human tissues and lead to variation in disease severity among patients. For this reason, this study aimed to take some SNPs in different COVID-19 patient cases to show the possible role of Angiotensin-Converting Enzyme-2 (ACE2) polymorphism in people that could have severe infections caused by SARS-CoV-2 by detecting different single nucleotide polymorphisms SNPs on this gene by PCR-sequencing. This cross-sectional study includes 100 diagnosed COVID-19 patients during a period between November and December 2021. The result revealed that three SNPs rs1463669655, rs746202722, and rs201035388 located on ACE-2 (GRCh38.p13) gene did not associate with the severity of COVID-19 disease because all patients have either the wildtype or the heteterotype allele as the following 0 % GG, 100 % AG, and 0% AA as the genotype distribution in severe cases, and the genotype distribution in non-severe cases was 0 % GG, 100 %AG, and 0 % AA and 100 % AA, 0 % AG, and 0% GG as the genotype distribution in severe cases, and the genotype distribution in non-severe cases was 100 % AA, 0 %AG, and 0 % GG and 100 % GG, 0 % GA, and 0% AA as the genotype distribution in severe cases, and the genotype distribution in non-severe cases was 100 % GG, 0 %GA, and 0 % AA for these three SNPs respectively. The ACE-2 angiotensin-converting enzyme gene was studied because of its active participation in the entry of the Coronavirus into the human body and its binding to alveolar cells and concluded that three SNPs rs1463669655, rs746202722, and rs201035388 located on ACE-2(GRCh38.p13) gene did not associate with the severity of COVID-19 disease.

Serum Ace and Ace I/D Polymorphism: Risk of Type 2 Diabetes with and Without Nephropathy in Pakistani Cohort

Objective: To find serum ACE (Angiotensin converting enzyme) level and the role of ACE I/D polymorphism with T2DM (Type 2 Diabetes Mellitus) among the Pakistani cohort.&#x0D; Methods: A total of 110 diagnosed T2DM patients and 100 normotensive healthy controls with an agerange of 35-65 years were randomly selected for this study. All cases were screened for the T2DM based on random and fasting blood sugar levels and confirmed by HbA1c test. Genomic DNA was extracted from peripheral blood samples by the Salting out method and ACE I/D polymorphism was genotyped using insertion-deletion polymorphism. A serum level of ACE was also determined. All statistical analysis was conducted using SPSS 16 and all values are significant at a p-value less than 0.05. Hardy Weinberg Equilibrium (HWE) was calculated for any deviation of allele frequencies from predicted. The Chi-square test was used to evaluate the association between ACE polymorphism and the risk of diabetes. The odds ratio along with a 95% confidence interval via binary logistics regression analysis was used to find out the diabetic risk associated with ACE genotyping.&#x0D; Results: The analysis showed higher ACE levels among T2DM patients with nephropathy (mean =158 ± 38.9) and without nephropathy (mean = 128.23 ± 46.8) as compared to controls (mean = 94.4± 28.6). No significant association (÷2 = 7.402, p-value=0.116) was observed between ACE genotyping and T2DM. However, those who have DD (O.R= 2.714, 95% CI=0.943-7.809) genotype of ACE polymorphism was at risk of diabetes but the results were non-significant. However, no risk was present at the diabetic nephropathy females.Conclusion: These outcomes propose that the ACE gene may not contribute to T2DM in the Pakistanicohort. However, ACE levels were higher among T2DM with and without nephropathy patients.

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection.

It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled "ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome"), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the ACE2 gene (including its alternative isoforms). Over the past 2 years, an impressive amount of new results have come to shed light on the role of ACE2 in the pathophysiology of COVID-19, requiring us to update our analysis. Genetic linkage studies have been reported that highlight a relationship between ACE2 genetic variants and the risk of developing hypertension. Currently, many research efforts are being undertaken to understand the links between ACE2 polymorphism and the severity of COVID-19. In this review, we update the state of knowledge on the polymorphism of ACE2 and its consequences on the susceptibility of individuals to SARS-CoV-2. We also discuss the link between the increase of angiotensin II levels among SARS-CoV-2-infected patients and the development of a cytokine storm associated microvascular injury and obstructive thrombo-inflammatory syndrome, which represent the primary causes of severe forms of COVID-19 and lethality. Finally, we summarize the therapeutic strategies aimed at preventing the severe forms of COVID-19 that target ACE2. Changing paradigms may help improve patients' therapy.

COVID-19 and aerobic exercise: possible role of angiotensin converting enzyme 2

The emergence and circulation of a novel coronavirus (2019-nCoV)—Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—set off a global health crisis. SARS-CoV-2 spreads faster than its two ancestors, SARS-CoV and MERS-CoV. Several modes of transmission have been identified: via respiratory droplets, contact with infected people or contaminated surfaces, and potentially, bioaerosols. Various countries have taken preventive measures that may include partial or total lockdowns lasting weeks. The physical inactivity associated with lockdowns may promote cardiometabolic or other diseases, while physical activity may play a critical role in preventing them. Here we develop the hypothesis of the involvement of aerosols in the contamination process, the role of angiotensin converting enzyme 2 (ACE2), the potential benefits and harm of physical activity during lockdowns, and we suggest directions for future research.

Abstract P117: MECHANISMS OF SIGNALING PATHWAYS TRIGGERED BY ANGIOTENSIN I CONVERTING ENZYME IN CHO ECA CELLS TREATED WITH CAPTOPRIL

Renin-Angiotensin System (RAS) is a hormonal system associated with hydroelectrolytic homeostasis and blood pressure control. Angiotensin II (Ang II) is the main and most potent biologically active product in the system, which is produced by the action of Angiotensin Converting Enzyme (ACE) on Ang I. Dysregulation of RAS is an important factor in the development and progression of cardiovascular/renal diseases and diabetes. Experiments and clinical practice have shown that the use of an ACE inhibitor (ACEi) is an effective treatment to attenuate hypertension and diabetic renal damage. In addition, recently the use of ACEi has also been associated with the activation of signaling pathways thus suggesting that ACE can act as a signal transductional molecule. The purpose of this study is to demonstrate the proteins that are differentially regulated when CHO-ECA cells are treated with the ACE inhibitor, captopril. The CHO-ACE cells were cultured in DMEM-SILAC medium in different media: Medium with light chain lysine (LV), medium with heavy chain lysine (P), and control (CT), with DMEM-High Glucose medium. At the 75% confluency, the cells were deprived of serum and then stimulated with captopril (1μM) or vehicle for 2 and 5 minutes (min). CHO-ACE cells were also cultured for the assay analysis of the Kinase Array. ACE activity was determined spectrofluorimetrically using ZPhe-His-Leu as substrate. With the SILAC medium, it was not possible to detect the differently modulated proteins by captopril. The kinase array demonstrated that some signaling pathways were not modulated after Captopril (eg, MSK1/2 and CREB). Other kinases were positively modulated after 2 min stimulation (eg, AMPKa1, HSP27, Akt 1/2/3 T308) and 5 min stimulation (STATa/b, HSP60, b-Catenin) with Captopril. Our screening also has shown that some kinases were negatively modulated following Captopril (eg, p53, PLC-γ1, Pyk2, eNOS). ACE activity in cell lysate group was inexpressive when treated with captopril. Our results expanded the repertoire of kinases modulated by the binding of Captopril to ACE, as well as, the role of ACE as a receptor and the modulation of signaling pathways triggered by this binding, which may imply in the treatment of hypertension.