Formation of angiotensin III by angiotensin-converting enzyme.
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ABSTRACT:
SUBMITTER: Chiu AT
PROVIDER: S-EPMC1172816 | biostudies-other | 1976 Apr
REPOSITORIES: biostudies-other
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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.
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Project description:The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 850 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 100 is Angiotensin-Converting Enzyme-2. Keywords: Angiotensin, angiotensin-converting enzyme 2 (ACE2), apelin, bradykinin, carboxypeptidase, cardiovascular, collectrin, renin-angiotensin system, SARS virus, shedding, transmembrane, vasoactive, zinc-binding motif.
| S-EPMC7150073 | biostudies-literature
Project description:Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (AngII) to form angiotensin-(1-7) (Ang-(1-7)), which generally opposes effects of AngII. AngII infusion into hypercholesterolemic male mice induces formation of abdominal aortic aneurysms (AAAs). This study tests the hypothesis that deficiency of ACE2 promotes AngII-induced AAAs, whereas ACE2 activation suppresses aneurysm formation.ACE2 protein was detectable by immunostaining in mice and human AAAs. Whole-body deficiency of ACE2 significantly increased aortic lumen diameters and external diameters of suprarenal aortas from AngII-infused mice. Conversely, ACE2 deficiency in bone marrow-derived cells had no effect on AngII-induced AAAs. In contrast to AngII-induced AAAs, ACE2 deficiency had no significant effect on external aortic diameters of elastase-induced AAAs. Because ACE2 deficiency promoted AAA formation in AngII-infused mice, we determined whether ACE2 activation suppressed AAAs. ACE2 activation by administration of diminazene aceturate (30 mg/kg per day) to Ldlr(-/-) mice increased kidney ACE2 mRNA abundance and activity and elevated plasma Ang-(1-7) concentrations. Unexpectedly, administration of diminazene aceturate significantly reduced total sera cholesterol and very low-density lipoprotein-cholesterol concentrations. Notably, diminazene aceturate significantly decreased aortic lumen diameters and aortic external diameters of AngII-infused mice resulting in a marked reduction in AAA incidence (from 73% to 29%). None of these effects of diminazene aceturate were observed in the Ace2(-/y) mice.These results demonstrate that ACE2 exerts a modulatory role in AngII-induced AAA formation, and that therapeutic stimulation of ACE2 could be a benefit to reduce AAA expansion and rupture in patients with an activated renin-angiotensin system.
| S-EPMC4250973 | 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:BackgroundAngiotensin (Ang)I is cleaved by angiotensin-converting enzyme (ACE) to generate AngII. The purpose of this study was to determine the roles of ACE in endothelial and smooth muscle cells in aortic aneurysms.Methods and Results:AngI infusion led to thoracic and abdominal aortic aneurysms in low-density lipoprotein receptor-deficient mice, which were ablated by ACE inhibition. Endothelial or smooth muscle cell-specific ACE deletion resulted in reduction of AngI-induced thoracic, but not abdominal, aortic dilatation.ConclusionsAngI infusion causes thoracic and abdominal aortic aneurysms in mice. ACE in aortic resident cells has differential effects on AngI-induced thoracic and abdominal aortic aneurysms.
| S-EPMC7301959 | 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