Disease relevance of ACE

• Our results suggest that increased cardiac ACE1 does not trigger but augments cardiac hypertrophy [1].
• Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy [1].
• Role of neutral endopeptidase and kininase II on substance P-induced increase in nasal obstruction in patients with allergic rhinitis [2].
• 1. The response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to inhibition of angiotensin I converting enzyme (kininase II) with captopril has been studied in patients with severe, treatment-resistant, malignant hypertension [3].
• CD10, CD13, and CD143 were significantly up-regulated in GCs and the lymph node metastases, confirming that they are important for the tumor cell biology [4].

Psychiatry related information on ACE

• APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease [5].
• Both 20 mg HYD/1000 mg ACET and MOR impaired psychomotor performance [6].

High impact information on ACE

• Angiotensin converting enzyme (encoded by the gene DCP1, also known as ACE) catalyses the conversion of angiotensin I to the physiologically active peptide angiotensin II, which controls fluid-electrolyte balance and systemic blood pressure [7].
• Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease [8].
• The diversity uncovered in DCP1 is comparable to that described for other regions in the human genome [7].
• We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems [9].
• The presence of captopril, an inhibitor of bradykinin degradation by kininase II, drastically potentiated parasitic invasion of HUVECs and CHO-B(2)R, but not of mock-transfected CHO cells, whereas the B(2)R antagonist HOE 140 or monoclonal antibody MBK3 to bradykinin blocked these effects [10].

Chemical compound and disease context of ACE

• Variation in the DCP1 gene, encoding the angiotensin converting enzyme ACE, is not associated with increased susceptibility to Alzheimer's disease [11].
• Ten of 26 patients with sepsis were given a combination of dexamethasone (0.15 mg/kg, intravenously, once on admission), colchicine (0.5 mg, orally, daily, for 3 days) and pentoxifylline (DCP) (400 mg, orally, daily, for 3 days), together with best medical therapy [12].
• In particular, the inhibition of angiotensin-converting enzyme, also known as kininase II, can protect against cardiac ischemia, putatively via accumulation of bradykinin [13].
• Possible evidence for this phenomenon was obtained by demonstrating that the hyperpermeability caused by the ascites could be blocked by Trasylol (known to inhibit bradykinin synthesis) and potentiated by captopril (a kininase II inhibitor) [14].
• HYD/ACET and MOR produced miosis [6].

Biological context of ACE

• Kininase II-type enzymes. Their putative role in muscle energy metabolism [15].
• When subjects were subdivided according to whether they possessed at least one copy of the APOE e4 allele, there were still no differences in DCP1 allele frequencies between cases and controls [11].
• The amino-terminal amino acid sequence and several internal peptide sequences of angiotensin I-converting enzyme (ACE; peptidyl-dipeptidase A, kininase II; EC 3.4.15.1) purified from human kidney were used to design oligonucleotide probes [16].
• Deviations from HWE may limit the comparability of study results and require clarification before drawing conclusions with respect to disease risk, health conditions, or longevity in association with DCP1 genotype [17].
• However, decreased binding of human spermatozoa to the oolemma of zonafree hamster oocytes after inhibition of ACE by captopril indicates that kininase II is involved in sperm-egg interactions [18].

Anatomical context of ACE

• Thus, in conclusion, heart and skeletal muscle membranes contain kininase II-type enzymes, but their activity depends on the species [15].
• Angiotensin-converting enzyme (CD143) is abundantly expressed by dendritic cells and discriminates human monocyte-derived dendritic cells from acute myeloid leukemia-derived dendritic cells [19].
• Angiotensin-1 perfusion of isolated hearts demonstrated a significant decrease in coronary artery flow compared with non-transgenic littermates, suggesting that the transgenic ACE1 is functional [1].
• To determine if the increased cardiac ACE1 actively plays a role or is merely the consequence of pathological changes in the process of cardiac hypertrophy, we generated a transgenic rat model with selective over-expression of human ACE1 in the cardiac ventricles [1].
• The gastric foveolar epithelium did not express CD10, CD13, or CD143, but the intestinal metaplasia demonstrated strong immunoreactivity at the brush border for all four ectopeptidases [4].

Associations of ACE with chemical compounds

• Our investigations started when synthetic bradykinin became available and we could characterize two enzymes that cleaved it: kininase I or plasma carboxypeptidase N and kininase II, a peptidyl dipeptide hydrolase that we later found to be identical with the angiotensin I converting enzyme (ACE) [20].
• Repeat measurements during captopril therapy showed a shift to the left of the BK/FBF, but not of the NP/FBF, dose-response curve, indicating effective vascular kininase II inhibition [21].
• Plasma bradykinin concentration did not change in response to SQ 20881, which also blocks kininase II [22].
• Inhibiting other substance P-degrading enzymes including kininase II (angiotensin-converting enzyme), serine proteases, and aminopeptidases did not affect the response to substance P [23].
• In contrast, the kininase II inhibitor captopril and the peptidase inhibitors leupeptin and bestatin had no effect [24].

Regulatory relationships of ACE

• There was no significant difference in the DCP1 allele or genotype frequencies between cases and controls when stratified by gender and APOE epsilon4 status [25].
• Northern blot analysis revealed that the ace1 gene was expressed much higher than the ace2 in all examined body parts [26].
• Serum tumour necrosis factor-alpha (TNF-alpha) levels were undetectable at 24 h compared with about 4 IU/ml (mean) in 16 similar control patients who were not given DCP (P < 0.06) [12].
• Angiotensin converting enzyme (kininase II) mRNA production and enzymatic activity in human peripheral blood monocytes are induced by GM-CSF but not by other cytokines [27].

Other interactions of ACE

• The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity [28].
• The presence of the AGTR1 C allele is a strong independent determinant of aortic stiffness, whereas presence of the ACE 1 allele is weakly associated with increased stiffness [29].
• CONCLUSION: The increased levels of kininogen fractions, kallikreins, and kininase II in patient plasma and CSF indicate overactivity of the kinin system, suggesting intense kinin production [30].
• The common Arabian ancestors of the Egyptians, Spanish, Saudi, and Emirate had created a common pattern of distribution of some allelic variants ( DCP1 and CETP) [31].
• We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells [32].

Analytical, diagnostic and therapeutic context of ACE

• Angiotensin I-converting enzyme (ACE; CD143, Kininase II, EC 3.4.15.1) is known to be crucial for male fertility in animal models [33].
• Sequence analyses showed that both genes possess all the typical features of ace, and that Bgace1 is orthologous to the insect ace1 whereas Bgace2 is to the insect ace2 [34].
• The presence of CD143 was also investigated in the same BM samples by flow cytometry [35].
• Furthermore, site-directed mutagenesis of the serine residue at position 431 in ace1 from a pirimicarb-susceptible clone of A gossypii conferred insensitivity to pirimicarb [36].
• Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (MS) with ProteinChip Array technology, ACE1 and ACE2 activity could be measured using natural peptide substrates [37].

References