Angiotensin-Converting Enzyme-2
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ABSTRACT:
SUBMITTER: Clarke N
PROVIDER: S-EPMC7150073 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Angiotensin converting enzyme (ACE) is well known for its dual actions to convert inactive Ang I to active Ang II, and degrades active bradykinin (BK), which plays an important role in controlling blood pressure. Because it is the bottleneck step for the production of pressor Ang II, it was targeted pharmacologically in the 1970s. Successful ACE inhibitors such as captopril were produced to treat hypertension. Studies on domain-specific ACE inhibitors are continuing to produce effective hypertension-controlling drugs with fewer side effects. ACE2 was discovered in 2000 and it converts Ang II into Ang(1–7), thereby reducing the concentration of Ang II as well as increasing that of Ang(1–7), an important enzyme for Ang(1–7)/Mas receptor signaling. ACE2 also acts as the receptor in the lung for the coronavirus, causing the infamous severe acute respiratory syndrome (SARS) in 2003.
| S-EPMC8361046 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.
| S-EPMC7129862 | biostudies-literature
Project description:Angiotensin-converting enzyme inhibitors (ACE-I) are widely used in diseases, such as hypertension, congestive heart failure, and myocardial infarction. Although these drugs are well tolerated, one out of five patients discontinues ACE-I due to drug side effects, mainly chronic cough. However, the pathogenesis of ACE-I-induced cough remains controversial and requires further study. In this review, the mechanisms that are suggested in ACE-I-induced cough pathophysiology will be discussed in detail in light of the current literature.
| S-EPMC6340691 | biostudies-literature
Project description:ObjectiveTo assess the polymorphism of angiotensin converting enzyme (ACE) in ischemic stroke in an Egyptian sample.MethodsOne hundred subjects (70 ischemic stroke patients, and 30 healthy controls) were included in case control cross sectional study during the period from January 2017 to January 2018, at Neurology Department, Menufia University Hospital, Shibin EL-Kom, Egypt. Patients underwent complete neurological assessment, national institute health stroke scale (NIHSS), and Toast classification. All subjects underwent genotyping of ACE gene polymorphism.ResultsThere are 42.9% from the patients versus 33.3% from controls showed geno typing of Insertion/Deletion (I/D) and Allele D is more frequent regarding I allele in ischemic stroke patients but this difference did not reach significant level to be risk factor. The I/D polymorphism was the predominant type in SVS and LVS while DD was the predominant type in cardio-embolic one. There were no significant differences between NIHSS in different ACE gene polymorphism.ConclusionIn spite of ACE genotyping differences among Egyptian ischemic stroke patients, we cannot consider it a predisposing factor to stroke occurrence or severity.
| S-EPMC8015476 | biostudies-literature
Project description:RationaleHypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population.ObjectiveHomozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes.Method and resultsThe Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans.ConclusionCOVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes.
| S-EPMC7478439 | biostudies-literature
Project description:Aerobic exercise training leads to a physiological, nonpathological left ventricular hypertrophy; however, the underlying biochemical and molecular mechanisms of physiological left ventricular hypertrophy are unknown. The role of microRNAs regulating the classic and the novel cardiac renin-angiotensin (Ang) system was studied in trained rats assigned to 3 groups: (1) sedentary; (2) swimming trained with protocol 1 (T1, moderate-volume training); and (3) protocol 2 (T2, high-volume training). Cardiac Ang I levels, Ang-converting enzyme (ACE) activity, and protein expression, as well as Ang II levels, were lower in T1 and T2; however, Ang II type 1 receptor mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. Ang II type 2 receptor mRNA levels (220%) and protein expression (332%) were shown to be increased in T2. In addition, T1 and T2 were shown to increase ACE2 activity and protein expression and Ang (1-7) levels in the heart. Exercise increased microRNA-27a and 27b, targeting ACE and decreasing microRNA-143 targeting ACE2 in the heart. Left ventricular hypertrophy induced by aerobic training involves microRNA regulation and an increase in cardiac Ang II type 1 receptor without the participation of Ang II. Parallel to this, an increase in ACE2, Ang (1-7), and Ang II type 2 receptor in the heart by exercise suggests that this nonclassic cardiac renin-angiotensin system counteracts the classic cardiac renin-angiotensin system. These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, altering the expression of specific microRNAs targeting renin-angiotensin system genes. Together these effects might provide the additional aerobic capacity required by the exercised heart.
| S-EPMC3184458 | biostudies-literature
Project description:ImportanceThe renin-angiotensin system has been implicated in mood disorders. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the most commonly used medications, yet their effects on mental health outcomes, particularly suicide, are poorly understood. This study examined the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, it was speculated that ARBs would be associated with a higher risk of suicide than ACEIs.ObjectiveTo examine the association between suicide and exposure to ARBs compared with ACEIs.Design, setting, and participantsThis population-based nested case-control study of individuals aged 66 years and older used administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019. Cases were individuals who died by suicide within 100 days of receiving an ACEI or ARB. The date of death served as the index date. For each case, 4 controls were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All individuals received an ACEI or ARB within 100 days before the index date.ExposuresUse of an ACEI or ARB.Main outcomes and measuresConditional logistic regression was used to estimate odds ratios for the association between suicide and exposure to ARBs compared with ACEIs.ResultsNine hundred sixty-four cases were matched to 3856 controls. The median (interquartile range) age of cases and controls was 76 (70-82) years. Most cases (768 [79.7%]) and controls (3068 [79.6%]) were men. Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, 741 (74.0%) were exposed to ARBs, and 3115 (81.6%) were exposed to ACEIs. Compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98).Conclusions and relevanceThe use of ARBs may be associated with an increased risk of suicide compared with ACEIs. Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.
| S-EPMC6806420 | biostudies-literature
Project description:Angiotensin III is formed from des-Asp1 -angiotensin I by angiotensin-converting enzyme. The Km (11 muM) of the reaction is one-third of that for the conversion of angiotensin I into angiotensin II. As suggested by the Km values, bradykinin, peptide BPP9a and angiotensins II and III are better inhibitors of the formation of angiotensin II than of the formation of angiotensin III.
| S-EPMC1172816 | biostudies-other
Project description:Angiotensin (Ang)-converting enzyme 2 (ACE2) is a key enzyme in the metabolism of Ang II. XNT (1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one) and diminazene have been reported to exert various organ-protective effects, which are attributed to the activation of ACE2. To test the effect of these compounds, we studied Ang II degradation in vivo and in vitro as well as their effect on ACE2 activity in vivo and in vitro. In a model of Ang II-induced acute hypertension, blood pressure (BP) recovery was markedly enhanced by XNT (slope with XNT, -3.26±0.2 versus -1.6±0.2 mm Hg/min without XNT; P<0.01). After Ang II infusion, neither plasma nor kidney ACE2 activity was affected by XNT. Plasma Ang II and Ang (1-7) levels also were not significantly affected by XNT. The BP-lowering effect of XNT seen in wild-type animals was also observed in ACE2 knockout mice (slope with XNT, -3.09±0.30 versus -1.28±0.22 mm Hg/min without XNT; P<0.001). These findings show that the BP-lowering effect of XNT in Ang II-induced hypertension cannot be because of the activation of ACE2. In vitro and ex vivo experiments in both mice and rat kidney confirmed a lack of enhancement of ACE2 enzymatic activity by XNT and diminazene. Moreover, Ang II degradation in vitro and ex vivo was unaffected by XNT and diminazene. We conclude that the biological effects of these compounds are ACE2-independent and should not be attributed to the activation of this enzyme.
| S-EPMC4004079 | biostudies-literature
Project description:Angiotensin converting enzyme (ACE) is known for converting inactive angiotensin I into the potent vasoconstrictor angiotensin II, playing a critical role in blood pressure regulation. However, there is evidence that the dicarboxypeptidase activity of ACE is also essential for other physiological processes likely through processing of various peptide substrates. This study used mass spectrometry for the comprehensive detection and identification of natural substrates and products of ACE within the mouse plasma peptidome. The plasma peptidome of ACE KO mice was obtained through a multi-step purification process which included organic TCA precipitation as well as size exclusion and reversed phase chromatography. The obtained complex mixture of endogenous peptides was then subjected to in vitro cleavage by ACE. ACE-treated and untreated samples were then analyzed by LC/MS on an Orbitrap mass spectrometer, followed by alignment of MS1 data by Progenesis QI software. The MS1 signals that gained or lost intensity after treatment with ACE, were considered as possible products and substrates of ACE, respectively, and were selected for a targeted MS/MS analysis, and subsequently identified with PEAKS 8.5 and Proteome Discoverer software. Results. Close to 250 natural peptides were identified as possible substrates and products of ACE, demonstrating the high promiscuity of the enzyme. The use of internal standards as well as detection of some expected endogenous peptides, such as angiotensin II and bradykinin, supported the validity of the approach. Some of the newly identified substrates of ACE are known for their biological activities. For example, a fragment of complement C3, the 17-amino acid peptide C3f, exhibits spasminogenic activity and was processed by ACE. ACE cleavage of select peptides was further confirmed in vitro. Also, concentrations of ACE substrates in plasma from mice with variant genetic ACE domain backgrounds were determined by LC/MS using multiple reaction monitoring on a triple quadrupole mass spectrometer. The in vivo results were consistent with the in vitro results, in the sense that higher levels of the ACE substrates were observed when the respective processing domain was knocked out. The use of transgenic mice as well as ACE with single active domain allowed clarifying the ACE domain selectivity towards individual peptide substrates. This study resulted in creation of a library of substrates and products of ACE that can be further tested for their biological function and can help to elucidate the link between ACE and the numerous physiological effects attributed to its activity.
2019-11-12 | PXD010258 | Pride