Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-(1-7), a biologically active peptide of the renin-angiotensin system, is cardioprotective following ischemia/reperfusion and reduces cardiac hypertrophy. A recently discovered homolog of angiotensin converting enzyme (ACE), ACE2, is present in the heart and synthesizes angiotensin-(1-7) from angiotensin II. Cardiac ACE2 is elevated following inhibition of Ang II subtype 1 (AT(1)) receptors or blockade of angiotensin II production, suggesting that angiotensin-(1-7) plays a role in the beneficial effects of AT(1) receptor antagonists and ACE inhibitors in the heart. An increase in ACE2 activity and the production of angiotensin-(1-7) may thus represent a novel therapy for heart failure following myocardial infarction.
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PMID:Cardioprotective role for angiotensin-(1-7) and angiotensin converting enzyme 2 in the heart. 1980 91

It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of ACE, has direct effects on cardiac function. However, the role of ACE2 in the development of human heart failure is not fully understood. We evaluated the expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14 patients with end-stage heart failure. The amount of ACE2 mRNA positively correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01) but did not significantly correlate with LV ejection fraction or plasma brain natriuretic peptide levels. In conclusion, our data show that the up-regulation of the ACE2 gene in the LV myocardium of patients with severe heart failure was associated with the degree of LV dilatation and may thereby constitute an important adaptive mechanism to retard the progression of adverse LV remodeling.
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PMID:Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure. 2006 Jan 85

To explore the hypothesis that angiotensin II may play a role in the susceptibility to cerebral malaria (CM), we performed a genetic association study of malaria patients in Orissa, India analyzing three SNPs (ACE2 C-->T, iNOS C-->T, eNOS Glu-->Asp) and two I/D polymorphisms (ACE I/D and IL-4 B1/B2). Our results showed that the 'D' allele of ACE I/D polymorphism, responsible for increased Ang II production had a significant association with mild malaria and the ACE2 C-->T substitution had gender specific effect of possibly reduced expression of ACE2 in presence of 'T' allele in women leading to increased level of Ang II and hence protection against CM. Combined genotype analysis of eNOS Glu-->Asp substitution responsible for increased NO production in Plasmodium falciparum infected individuals and ACE I/D polymorphism also showed stronger association of (Glu-Asp+Asp-Asp/ID+DD) genotypes with mild malaria (P<0.0001). Whether by its antiplasmodial activity and/or by some unknown mechanisms, Ang II protects from susceptibility to cerebral malaria remains to be investigated. These genetic findings may contribute to the understanding of malaria pathogenesis.
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PMID:Gene polymorphisms in angiotensin I converting enzyme (ACE I/D) and angiotensin II converting enzyme (ACE2 C-->T) protect against cerebral malaria in Indian adults. 2011 48

Apelin is a peptide that has been identified as the endogenous ligand for the receptor APJ. The apelin/APJ system may be an important factor in the regulation of vascular tone and cardiovascular function. Studies on cultured cells and small animal models have revealed that apelin and APJ are localized in cardiomyocytes and vascular cells. The infusion of apelin affects vascular tone and blood pressure, with both central and peripheral actions. In clinical conditions such as heart failure and atherosclerosis, the gene expression of APJ and apelin, as well as the levels of circulating apelin, may be altered. The only known active homolog of ACE, ACE2, hydrolyzes apelin with similar potency to angiotensin II and, therefore, is responsible for the degradation of both peptides. Emerging data on a potential interaction between the two pathways suggest that the function of apelin/APJ in the vasculature may be relevant to cardiovascular disease, and identifying how this system is regulated could be useful clinically.
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PMID:Apelin and ACE2 in cardiovascular disease. 2017 40

Numerous studies have suggested that angiotensin peptides modulate the expression of angiotensin converting enzyme II (ACE2) in the cardiovascular system, but the molecular mechanisms remain poorly understood. In the present study, human cardiac fibroblasts (HCF) were used to test the regulatory effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on ACE2 expression. The results show that Ang II upregulates ACE2 expression. This action is modulated through activation of Ang II type 1 receptor (AT1R). Ang II-mediated ACE2 upregulation was blocked by antagonists of AT1R and ERK-MAPK signaling pathways. Additionally, Ang-(1-7) increased ACE2 expression, and this upregulation was inhibited by Ang-(1-7) Mas receptor blockade. Our results further reveal that the activation of p-ERK1/2 proteins plays a critical role in upregulating ACE2 in Ang-(1-7)-stimulated HCF cells. This effect occurs independently of the Ang II-AT1R signaling pathway. In conclusion, we propose that Ang II-upregulated ACE2 may increase Ang-(1-7) formation from Ang II, and that ACE2 expression is further enhanced by Ang-(1-7) in a positive feedback loop.
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PMID:Regulation of angiotensin converting enzyme II by angiotensin peptides in human cardiofibroblasts. 2034 4

Milk-based drinks containing casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown to possess antihypertensive and vascular endothelium-protecting properties in hypertensive animal models. Furthermore in clinical intervention trials they reduce blood pressure and arterial stiffness. The exact mechanisms are not known, but inhibition of angiotensin converting enzyme 1 (ACE1) has been suggested mainly to mediate these beneficial effects. The present study investigated the in vitro effects of three tripeptides: Ile-Pro-Pro, Val-Pro-Pro and leqcine-proline-proline (Leu-Pro-Pro) on four renin-angiotensin system enzymes: ACE1, ACE2, chymase, and cathepsin G. Also their effects on arginase I, a critical enzyme in L-arginine-nitric oxide pathway, were studied. It was shown, apparently for the first time, that the inhibitory effects of Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro on ACE1 at micromolar concentrations are competitive in nature. Therefore the efficacy of inhibition is largely dependent on the amount of substrate present. Inhibition of ACE2 and arginase I was reached only at concentrations three orders of magnitude greater. No inhibition of chymase and cathepsin G was observed by the tripeptides. The findings support the hypothesis that Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro act favourably on blood pressure mainly by selective inhibition of ACE1.
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PMID:Effects of milk casein-derived tripeptides Ile-Pro-Pro, Val-Pro-Pro, and Leu-Pro-Pro on enzymes processing vasoactive precursors in vitro. 2048 67

AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT1 receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P<0.01) and renal Ang-(1-7) was decreased substantially (P<0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased the renal mRNA expression of renin (P<0.05), AT1 receptors (P<0.001) and ACE2 (P<0.05). At 2 and 4 h of reperfusion, renal ACE activity was reduced (P<0.05). On the other hand, renal expression of the Mas receptor was greatly increased at 4 h of reperfusion (P<0.01), which was confirmed by immunohistochemical and Western blot analysis. In conclusion, increased renal expression of the Mas receptor associated with changes in the RAS (renin-angiotensin system)-related peptidases support an important role for the ACE2-Ang-(1-7)-Mas axis in AKI.
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PMID:ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats. 2052 71

The renin-angiotensin system plays an important role in various physiological and pathophysiological regulatory mechanisms. Within the past few years, the classical concept of a linear enzymatic cascade has experienced substantial changes. A parallel counterregulatory axis has been identified which involves the angiotensin converting enzyme homologue ACE2, angiotensin (1-7), and receptors Mas. The research in prorenin and its non-proteolytic activation has greatly advanced after the discovery of cellular receptors (P)RR; binding of renin or prorenin to these receptors not only facilitates angiotensin generation, but at the same time activates specific signal transduction pathways. The long-term search for clinically useful direct renin inhibitors has recently succeeded with the new antihypertensive drug aliskiren. While beneficial effects of aliskiren on some markers of cardiovascular and renal diseases have been proved in large clinical studies, important questions remain to be solved.
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PMID:[Renin, prorenin, and the direct renin inhibitor aliskiren]. 2066 66

The kidney is an important target for the actions of the renin-angiotensin system (RAS) and this tissue contains a complete local RAS that expresses the bioactive peptides angiotensin II (ANG II) and Ang-(1-7). We find both angiotensin type 1 (AT(1)R) and type 2 (AT(2)R) receptors expressed on renal nuclei that stimulate reactive oxygen species and nitric oxide (NO), respectively. Since Ang-(1-7) also exhibits actions within the kidney and the Ang-(1-7)/Mas receptor protein contains a nuclear localization sequence, we determined the expression of Ang-(1-7) receptors in nuclei isolated from the kidneys of young adult sheep. Binding studies with (125)I-[Sar(1)Thr(8)]-ANG II revealed sites sensitive to the Ang-(1-7) antagonist [d-Ala(7)]-Ang-(1-7) (DALA, A779), as well as to AT(2) and AT(1) antagonists. Incubation of Ang-(1-7) [10(-15) to 10(-9) M] with isolated cortical nuclei elicited a dose-dependent increase in the fluorescence of the NO indicator [4-amino-5-methylamino-2',7']-difluorofluorescein diacetate. The NO response to Ang-(1-7) was abolished by the NO inhibitor N-nitro-l-arginine methyl ester and DALA, but not the AT(1) antagonist losartan or the AT(2) blocker PD123319. Immunofluorescent studies utilizing the Ang-(1-7)/Mas receptor antibody revealed immunolabeling of the proximal tubules but not staining within the glomerulus in cortical sections of the sheep kidney. In the nuclear fraction of isolated proximal tubules, immunoblots revealed the precursor angiotensinogen and renin, as well as functional activity for ACE, ACE2, and neprilysin. We conclude that renal nuclei express Ang-(1-7)/Mas receptors that are functionally linked to NO formation. The marked sensitivity of the intracellular NO response to Ang-(1-7) implicates a functional role of the Ang-(1-7) axis within the nucleus. Moreover, evidence for the precursor and enzymatic components of the RAS within the nuclear compartment of the proximal tubules provides a potential pathway for the intracellular generation of Ang-(1-7).
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PMID:Nuclear angiotensin-(1-7) receptor is functionally coupled to the formation of nitric oxide. 2081 Jun 9

The influence of angiotensin II and angiotensin (1-17) on cell volume and on the activation of ionic channels including the swelling-dependent chloride channel was reviewed. Particular emphasis was given to the influence of the balance between the ACE-angiotensin II and of the ACE2-angiotensin (1-7)-Mas receptor axis on heart cell volume regulation and on the swelling-dependent chloride current. The implications for myocardial ischemia and cardiac arrhythmias are discussed.
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PMID:Angiotensin (1-7) reduces the cell volume of swollen cardiac cells and decreases the swelling-dependent chloride current. Implications for cardiac arrhythmias and myocardial ischemia. 2081 13


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