ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors

2002 ◽  
Vol 80 (4) ◽  
pp. 346-353 ◽  
Author(s):  
Anthony J Turner ◽  
Sarah R Tipnis ◽  
Jodie L Guy ◽  
Gillian I Rice ◽  
Nigel M Hooper
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Catalytic Domain ◽  
Signal Sequence ◽  
Tissue Response ◽  
Binding Motif ◽  
Converting Enzyme ◽  
Thermus Aquaticus ◽  
Considerable Homology

A human zinc metalloprotease (termed ACEH or ACE2) with considerable homology to angiotensin- converting enzyme (ACE) (EC 3.4.15.1) has been identified and subsequently cloned and functionally expressed. The translated protein contains an N-terminal signal sequence, a single catalytic domain with zinc-binding motif (HEMGH), a transmembrane region, and a small C-terminal cytosolic domain. Unlike somatic ACE, ACEH functions as a carboxypeptidase when acting on angiotensin I and angiotensin II or other peptide substrates. ACEH may function in conjunction with ACE and neprilysin in novel pathways of angiotensin metabolism of physiological significance. In contrast with ACE, ACEH does not hydrolyse bradykinin and is not inhibited by typical ACE inhibitors. ACEH is unique among mammalian carboxypeptidases in containing an HEXXH zinc motif but, in this respect, resembles a bacterial enzyme, Thermus aquaticus (Taq) carboxypeptidase (EC 3.4.17.19). Collectrin, a developmentally regulated renal protein, is homologous with the C-terminal region of ACEH but has no similarity with ACE and no catalytic domain. Thus, the ACEH protein may have evolved as a chimera of a single ACE-like domain and a collectrin domain. The collectrin domain may regulate tissue response to injury whereas the catalytic domain is involved in peptide processing events.Key words: ACEH, ACE2, metalloprotease, collectrin, carboxypeptidase, angiotensin II.

scholarly journals Maximally Recommended Doses of Angiotensin-Converting Enzyme (ACE) Inhibitors Do Not Completely Prevent ACE-Mediated Formation of Angiotensin II in Chronic Heart Failure

Circulation ◽  
2000 ◽  
Vol 101 (8) ◽  
pp. 844-846 ◽  
Author(s):  
Ulrich P. Jorde ◽  
Pierre V. Ennezat ◽  
Jay Lisker ◽  
Vanarani Suryadevara ◽  
Jason Infeld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Chronic Heart Failure ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Converting Enzyme

ACE Inhibitor—Versus Angiotensin II Blocker–Induced Cough and Angioedema

1998 ◽  
Vol 32 (10) ◽  
pp. 1060-1066 ◽  
Author(s):  
George B Pylypchuk
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Data Sources ◽  
Published Data ◽  
Converting Enzyme ◽  
Medline Search ◽  
Receptor Blockers ◽  
Comparative Trials

OBJECTIVE: To compare the tolerability of angiotensin-converting enzyme (ACE) inhibitors with that of angiotensin II (AII)-receptor blockers and the incidence of cough and angioedema associated with their use through review of published data. DATA SOURCES: References were identified through a MEDLINE search of articles published between January 1975 and April 1997. Bibliographies of pertinent references were also reviewed. RESULTS: Results of placebo-controlled and comparative trials of the AII blockers demonstrate that they are at least as effective as ACE inhibitors for hypertension, but exhibit an incidence of cough and absent or rare angioedema like that of placebo. CONCLUSIONS: In the 10 comparative trials described, all reported a lower incidence of cough with AII blockers than with ACE inhibitors. Angioedema was not reported in the comparative trials described.

Angiotensin II antagonist valsartan in the treatment of arterial hypertension

1998 ◽  
Vol 79 (3) ◽  
pp. 232-233
Author(s):  
A. S. Galyavich
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Arterial Hypertension ◽  
Ace Inhibitors ◽  
Years Of Experience ◽  
Converting Enzyme ◽  
Angiotensin Ii Antagonist

20 years of experience with the use of angiotensin-converting enzyme (ACE) inhibitors in the clinic has shown that in some patients with arterial hypertension (AH) drugs of this group are ineffective. In addition, during treatment with ACE inhibitors, the following fact is also observed: after a certain period of lowering blood pressure (BP) against the background of their intake, its increase is again noted, despite an increase in the dose of the drug

scholarly journals The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Myla E. Moretti ◽  
Daniela Caprara ◽  
Irina Drehuta ◽  
Emily Yeung ◽  
Stefanie Cheung ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
First Trimester ◽  
Angiotensin Ii Receptor Blockers ◽  
Healthy Controls ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Increased Risk ◽  
Receptor Blockers

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P<0.001for both variables). There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P<0.001). These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage.

New fACEs to the Renin-Angiotensin System

Physiology ◽  
2005 ◽  
Vol 20 (2) ◽  
pp. 91-95 ◽  
Author(s):  
Ingrid Fleming ◽  
Karin Kohlstedt ◽  
Rudi Busse
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Angiotensin Converting Enzyme ◽  
Kidney Function ◽  
Ace Inhibitors ◽  
Renin Angiotensin System ◽  
Signaling Cascade ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Beneficial Effects

Inhibition of the angiotensin-converting enzyme (ACE) protects against the progression of several cardiovascular diseases. Recent evidence suggests that some of the beneficial effects of ACE inhibitors can be attributed to the activation of a distinct ACE signaling cascade rather than to the changes in angiotensin II and bradykinin levels. Moreover, at least one other ACE homolog (ACE2) plays a significant role in the regulation of heart and kidney function.

Use of Angiotensin-Converting Enzyme Inhibitors in Heart Failure

1994 ◽  
Vol 10 (4) ◽  
pp. 156-163 ◽  
Author(s):  
Bisrat Hailemeskel ◽  
Vlncent F. Mauro
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Ejection Fraction ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Current Data ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Reduced Ejection Fraction ◽  
English Language Journal

Objective: To review the literature discussing the use of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure. Data Sources: English-language journal articles. Study Selection: Representative articles discussing the effects of ACE inhibitors on hemodynamics, symptoms, and survival. Data Extraction: Studies selected for review in the text were based on study design and clinical endpoints. Data Synthesis: Heart failure results in a series of compensatory responses that, although effective acutely, are ultimately maladaptive. A major mediator in this process is angiotensin II. The production of angiotensin II is dependent on the ACE. Inhibition of this enzyme by ACE inhibitors results in fewer symptoms, improved hemodynamic function, and prolonged survival in patients with heart failure. Conclusions: ACE inhibitors are beneficial in improving the survival of patients with symptomatic heart failure and of patients who have recently had an acute myocardial infarction (MI) and subsequently have a reduced ejection fraction. There appears to be no advantage for immediately initiating ACE-inhibitor therapy within the first few hours of an MI episode. With respect to patients with a reduced ejection fraction without symptoms of heart failure, current data suggest that ACE inhibitors delay the onset of symptoms of heart failure, reduce the need for hospitalization, and may possibly improve survival.

scholarly journals ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Andrew M. South ◽  
Tammy M. Brady ◽  
Joseph T. Flynn
Keyword(s):  
Cardiovascular Disease ◽  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Receptor Blockers ◽  
Adults And Children

Potential but unconfirmed risk factors for coronavirus disease 2019 (COVID-19) in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, ACE (angiotensin-converting enzyme) inhibitors, and Ang II (angiotensin II) receptor blockers. Coronavirus binding to ACE2 (angiotensin-converting enzyme 2), a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus, but the reasons are unclear. This review will highlight the relationship of COVID-19 with hypertension, use of ACE inhibitors and Ang II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the ACE 2/Ang-(1–7) pathway in children and the clinical evidence for how ACE inhibitors and Ang II receptor blockers affect this important pathway. Given the importance of the ACE 2/Ang-(1–7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe COVID-19.

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