Distribution Of Angiotensin-converting Enzyme Research Articles

Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human

Purpose Coronavirus disease 2019 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 have a higher risk of being infected by severe acute respiratory syndrome coronavirus 2. The susceptibility of coronavirus disease 2019 in patients with chronic diseases, especially in different tissues of ocular hypertension eyes like glaucoma, is not yet known. Methods An ocular hypertension model was established by laser photocoagulation in rhesus monkeys. The expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in three ocular hypertension eyes and the three control eyes were analyzed using immunofluorescence. Results No difference was observed between ocular hypertension and control eyes in the expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in the conjunctival epithelium, corneal epithelium, and ciliary muscle. In ocular hypertension eyes and control eyes, angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression were both observed in the retina. Angiotensin-converting enzyme 2 staining of retinal ganglion cells was found to be significantly higher in ocular hypertension eyes than in control eyes. However, there was no difference in angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression in retinal vessels and choroidal vessels between ocular hypertension and control eyes. In our study, the expression and distribution of angiotensin-converting enzyme 2 and TMPREE2 in human retina were similar to that of non-human primates as expected. Conclusion Our study confirmed that angiotensin-converting enzyme 2 and transmembrane protease serine type 2 were expressed widely in rhesus monkey eyes. When compared with controls eyes, the expression of angiotensin-converting enzyme 2 was higher in the retinal ganglion cells in ocular hypertension eyes, suggesting that high ocular pressure may affect the patients’ ocular susceptibility to severe acute respiratory syndrome coronavirus 2 infection.

Distribution of Coronavirus Receptors in the Swine Respiratory and Intestinal Tract.

Simple SummaryOverall, viral receptors are cell surface molecules that allow for virus binding and cell entry leading to productive infection. The presence and distribution of these receptors across tissues can determine susceptibility and the outcome of the infection. This study demonstrates the presence of the main protein receptors used by different coronaviruses in the respiratory and intestinal tract of pigs. The present study has important implications for the development of research models and for the assessment of the potential risk and introduction of coronaviruses into the swine population.Coronaviruses use a broad range of host receptors for binding and cell entry, essential steps in establishing viral infections. This pilot study evaluated the overall distribution of angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and dipeptidyl peptidase 4 (DPP4) receptors in the pig respiratory and intestinal tract. All the receptors evaluated in this study were expressed and differentially distributed through the respiratory and intestinal tract. The presence and expression levels of these receptors could determine susceptibility to coronavirus infections. This study may have important implications for the development of research models and the assessment of the potential risk and introduction of novel coronaviruses into the swine population.

Potential role of astrocyte angiotensin converting enzyme 2 in the neural transmission of COVID-19 and a neuroinflammatory state induced by smoking and vaping

BackgroundKnowledge of the entry receptors responsible for SARS-CoV-2 is key to understand the neural transmission and pathogenesis of COVID-19 characterized by a neuroinflammatory scenario. Understanding the brain distribution of angiotensin converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, remains mixed. Smoking has been shown as a risk factor for COVID-19 severity and it is not clear how smoking exacerbates the neural pathogenesis in smokers.MethodsImmunohistochemistry, real-time PCR and western blot assays were used to systemically examine the spatial-, cell type- and isoform-specific expression of ACE2 in mouse brain and primary cultured brain cells. Experimental smoking exposure was conducted to evaluate the effect of smoking on brain expression.ResultsWe observed ubiquitous expression of ACE2 but uneven brain distribution, with high expression in the cerebral microvasculature, medulla oblongata, hypothalamus, subventricular zones, and meninges around medulla oblongata and hypothalamus. Co-staining with cell type-specific markers demonstrates ACE2 is primarily expressed in astrocytes around the microvasculature, medulla oblongata, hypothalamus, ventricular and subventricular zones of cerebral ventricles, and subependymal zones in rhinoceles and rostral migratory streams, radial glial cells in the lateral ventricular zones, tanycytes in the third ventricle, epithelial cells and stroma in the cerebral choroid plexus, as well as cerebral pericytes, but rarely detected in neurons and cerebral endothelial cells. ACE2 expression in astrocytes is further confirmed in primary cultured cells. Furthermore, isoform-specific analysis shows astrocyte ACE2 has the peptidase domain responsible for SARS-CoV-2 entry, indicating astrocytes are indeed vulnerable to SARS-CoV-2 infection. Finally, our data show experimental tobacco smoking and electronic nicotine vaping exposure increase proinflammatory and/or immunomodulatory cytokine IL-1a, IL-6 and IL-5 without significantly affecting ACE2 expression in the brain, suggesting smoking may pre-condition a neuroinflammatory state in the brain.ConclusionsThe present study demonstrates a spatial- and cell type-specific expression of ACE2 in the brain, which might help to understand the acute and lasting post-infection neuropsychological manifestations in COVID-19 patients. Our data highlights a potential role of astrocyte ACE2 in the neural transmission and pathogenesis of COVID-19. This also suggests a pre-conditioned neuroinflammatory and immunocompromised scenario might attribute to exacerbated COVID-19 severity in the smokers.

Evaluation of mid- and long-term impact of COVID-19 on male fertility through evaluating semen parameters.

BackgroundThe coronavirus disease 2019 (COVID-19) has spread worldwide with alarming levels of spread and severity. The distribution of angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) from bioinformatics evidence, the autopsy report for COVID-19 and the published study on sperm quality indicated COVID-19 could have a negative impact on male fertility. However, whether the negative impact of COVID-19 on male fertility is persistent remains unknown, which requires long-term follow-up investigation.MethodsSemen samples were collected from 36 male COVID-19 patients with a median recovery time of 177.5 days and 45 control subjects. Then, analysis of sperm quality and alterations of total sperm number with recovery time were performed.ResultsThere was no significant difference in semen parameters between male recovered patients and control subjects. And the comparisons of semen parameters between first follow-up and second follow-up revealed no significant difference. In addition, we explored the alterations of sperm count with recovery time. It showed that the group with recovery time of ≥120 and <150 days had a significantly lower total sperm number than controls while the other two groups with recovery time of ≥150 days displayed no significance with controls, and total sperm number showed a significant decline after a recovery time of 90 days and an improving trend after a recovery time of about 150 days.ConclusionsThe sperm quality of COVID-19 recovered patients improved after a recovery time of nearly half a year, while the total sperm number showed an improvement after a recovery time of about 150 days. COVID-19 patients should pay close attention to the quality of semen, and might be considered to be given medical interventions if necessary within about two months after recovery, in order to improve the fertility of male patients as soon as possible.

ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) in human beings, has caused a serious public health issue.1 Attention to pancreatic injury is lacking, which may impact patients' prognosis. In this study, we explored the expression and distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in the pancreas. Combined with clinical data, we showed that pancreatic injury can occur in some COVID-19 patients.

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2).1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure,2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.

Abstract 092: Uterine Artery Dysfunction in ACE2 Deficient Mice is Associated with Placental Hypoxia and Reduced Umbilical Flow

Intrauterine fetal growth restriction (IUGR), one of the serious complications of pregnancy, increases the risk for perinatal morbidity and mortality, and cardiovascular and renal abnormalities later in life. The components of the renin-angiotensin system (RAS) are important mediators of uteroplacental vasculature during pregnancy. The distribution of angiotensin converting enzyme 2 (ACE2), a key enzyme of the RAS, is described in the invading and intravascular trophoblasts, decidual cells and in the umbilical cord. Deletion of ACE2 restricts fetal weight gain and reduces fetal-to-placental weights ratio. ACE2 deficiency results in augmented uterine artery contractility to Ang II at mid-gestation. In this study we determined whether uterine artery dysfunction is associated with placental abnormalities in ACE2 KO mice at mid-gestation. Systolic blood pressures were higher in pregnant ACE2 KO vs. C57BL/6 wild type (WT) (102.3±5.1 vs. 85.1±1.9 mmHg). Urinary protein excretion, serum creatinine, mean kidney or heart weights were not different in ACE2 KO vs. WT. Fetal weight, normalized to tibia length, and pup-to-placental weight ratio were lower in ACE2 KO vs. WT (p&lt;0.05). A higher sensitivity to Ang II (pD 2 8.64±0.04 vs. 8.5±0.03, p&lt;0.05) concomitantly with a greater active uterine arterial tension tested as the response to KCl 75 mM (1.90±0.15 vs. 1.13±0.12 mN/mm, p&lt;0.05) were associated with lower Ang II receptor 2 (AT2R) protein expression (0.2±0.01 vs. 0.4±0.01, p&lt;0.05) in uterine arteries from pregnant ACE2 KO. In the placenta, trophoblast invasion as assessed by the distribution of cytokeratin in trophospongium and decidual areas was not different between ACE2 KO and WT mice. The staining for pimonidazole, a marker of placental hypoxia, was significantly increased in the trophospongium and placental labyrinth of the ACE2 KO vs. WT (p&lt;0.05). Umbilical artery velocities measured using VEVO 2100 ultrasound were lower in the ACE2 KO vs. WT mice (82.2±13.1 vs. 162.6±35.4 mm/s, p&lt;0.05). In summary, ACE2 deficiency induces uterine artery dysfunction associated with placental hypoxia and reduced umbilical flow. These changes develop before the major growth of fetus occurs and may contribute to the exacerbation of IUGR in the ACE2 KO mice.

P2‐024: Relationship between CSF and plasma proteomic data in the ADNI‐1 cohort

Recent efforts in proteome-based biomarker discovery for Alzheimer's disease (AD) identified a set of novel biomarkers from cerebrospinal fluid (CSF) and plasma [1,2]. Although CSF and plasma are separated by the blood-brain barrier and blood-CSF barrier, some analytes from both compartments have shown efficacy in classification of AD. However, the relationship between matched proteomic markers from CSF and plasma has not been studied in detail [3]. We investigated the relationship between plasma and CSF proteomic data sets using a Rules Based Medicine (RBM) panel available in the Alzheimer's Disease Neuroimaging Initiative (ADNI). 76 quality-controlled CSF and plasma analytes from the ADNI Biomarker Core were selected and analyzed for 261 participants (47 healthy control (HC), 146 patients with mild cognitive impairment (MCI), 68 AD). Many analytes were log-transformed to approximate normality within each diagnostic group and 13 analytes were differently processed. Therefore, we used the Spearman rank order correlation [4] to assess this relationship. Correlations between matched markers from CSF and plasma range from 0.00 1 to 0.89 for all samples. Tables 1 and 2 show the maximum and average correlation coefficients and top 10 correlations for all samples. Distribution of correlation coefficients for 76 analytes is shown in the descending order of coefficients for all samples in Figure 1. In Figure 2, distribution of angiotensin-converting enzyme (a) and clusterin (b) is shown and the correlation within each diagnostic group varies. Leptin from CSF and plasma was highly correlated with each other, consistent with previous findings [5]. Distribution of correlation coefficients. Analytes are sorted by the absolute value of correlation coefficients for all subjects in a decreasing order from left to right in x-axis. The individual correlation coefficients for some analytes are different by diagnosis. Zero correlation is highlighted by magenta dash-dotted line. Scatter plots of (a) Angiotensin-Coverting Enzyme and (b) Clusterin. X –axis represents CSF measure and y-axis plasma measure. Diagnostic groups are drawn by different colors (AD-red, MCI-blue, HC-green). The individual correlation coefficients within diagnostic groups are different. Correlation coefficients for all samples and within each diagnostic group show a similar trend and average correlations do not differ by diagnosis. Individual correlation coefficients for some analytes differ by diagnosis. These results warrant follow-up that may enhance understanding of the relationships of proteins across the blood-brain barrier and blood-CSF barrier and the role of compartmental differences at various stages of AD.

The Role of ACE I/D Gene Mutations in The Etiology of Buergers’s Disease

Thromboangiitis obliterans (TAO), which is also known as Buerger’s disease, is a disease characterized by segmental inflammation together with vasoactive phenomena in the arteries and veins of the extremities. In the present study, the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene mutations, which is known to be involved in vasodysfunction, and TAO was determined. Because of this relationship, it was aimed to determine whether the distribution of angiotensin-converting enzyme (ACE) insertion / deletion (I / D) gene mutations in patients with Thromboangiitis obliterans (TAO) is different from healthy subjects in the control group. Eighty patients who were previously diagnosed with TAO were included in the study. The patients were determined based on Olin’s criteria. The control group consisted of 88 healthy volunteers. DNA isolation was performed by venous blood from the patients in both groups. The DNAs were amplified via polymerase chain reaction (PCR) using appropriate primers, the amplicons were eluted by running in 1% agarose gel, and defined via staining. In addition to the signifi cant difference between the patient and control groups in terms of age and smoking due to the selection criteria (Olin’s criteria), a statistically significant difference was also determined between the groups in terms of the distribution of the ACE I/D gene polymorphism. The significant difference between groups with respect to the ACE I/D polymorphism, together with the smokinglike effects of ACE on the cardiovascular system, reveal a consequence which should not be neglected.

The relation of adiponectin and tumor necrosis factor α levels between endothelial nitric oxide synthase, angiotensin-converting enzyme, transforming growth factor β, and tumor necrosis factor α gene polymorphism in adrenal incidentalomas

The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-alpha, transforming growth factor (TGF)-beta genes polymorphisms, TNF-alpha, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). There was statistically significant difference between TNF-alpha levels of patient and controls (p=0.048). We have not detected the connection between TGF-beta, TNF-alpha, ACE, eNOS gene polymorphism with serum TNF-alpha and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. According to different cases of eNOS, TGF-beta, ACE, and TNF-alpha gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

No association found between the insertion/deletion of a 287-bp alu repeat sequence within intron 16 of the angiotensin-I-converting enzyme (ACE) gene in Mexican patients and binary restenosis after coronary stenting

Background It has been suggested that the incidence of coronary restenosis after a percutaneous coronary intervention is much higher in patients with a 287-bp alu repeat sequence within intron 16 of the angiotensin-I-converting enzyme (ACE) gene (deletion allele) than in others, but published studies are conflicting. Methods The presence (insertion) or absence (deletion) of a 287-bp alu repeat sequence within intron 16 of the ACE gene ( I/D polymorphism) was analyzed by polymerase chain reaction in a group of 168 patients with coronary artery disease who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. Results Distribution of angiotensin converting enzyme I/D polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made considering the type of stent implanted. On the other hand, the whole group of coronary artery disease patients showed increased frequencies of the D allele ( p = 0.00001, OR = 2.17, 95% CI = 1.49–3.16) and ID genotype ( p = 0.0002, OR = 2.58, 95%CI = 1.49–4.47) when compared to healthy controls. Conclusions Genetic variations of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican mixed racial ancestry individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

The pathology of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV, in the respiratory tracts of these species is unknown. We observed SARS-CoV antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ACE2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. All infected cats and ferrets had diffuse alveolar damage associated with SARS-CoV antigen expression. A novel SARS-CoV-associated lesion was tracheo-bronchoadenitis in cats. SARS-CoV antigen expression occurred mainly in type I and II pneumocytes and serous cells of tracheo-bronchial submucosal glands of cats and in type II pneumocytes of ferrets. ACE2 expression occurred mainly in type I and II pneumocytes, tracheo-bronchial goblet cells, serous epithelial cells of tracheo-bronchial submucosal glands in cats, and type II pneumocytes and serous epithelial cells of tracheo-bronchial submucosal glands in ferrets. In conclusion, the pathology of SARS-CoV infection in cats and ferrets resembles that in humans except that syncytia and hyaline membranes were not observed. The identification of tracheo-bronchoadenitis in cats has potential implications for SARS pathogenesis and SARS-CoV excretion. Finally, these results show the importance of ACE2 expression for SARS-CoV infection in vivo: whereas ACE2 expression in type I and II pneumocytes in cats corresponded to SARS-CoV antigen expression in both cell types, expression of both ACE2 and SARS-CoV antigen in ferrets was limited mainly to type II pneumocytes.

ACE gene insertion/deletion polymorphism in childhood idiopathic nephrotic syndrome

The aim of this study was to determine the distribution of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its effects on clinical, laboratory, histological findings, treatment responses and progression to end-stage renal disease in childhood idiopathic nephrotic syndrome (NS). 227 children diagnosed with idiopathic NS were included in the study. Eighty-three of patients were steroid resistant and 77 of patients were focal segmental glomerulosclerosis. The control group was consisted of 287 unrelated healthy adult volunteers. ACE gene I/D polymorphism were analyzed by using PCR based method. In the entire group of children with NS, the frequencies of the II, ID, and DD genotypes of ACE gene were 13.7%, 38.3% and 48%, respectively. D allele frequency was higher in NS group than control group (0.67 vs. 0.56, p=0.001). Percentage of frequent relapser patients was found more frequently in ID or DD genotype (38.7%) than II genotype (15%) when only steroid sensitive patients were evaluated (p=0.045). The D-allele frequency was 0.65, 0.69 and 0.68 respectively in focal segmental glomerulosclerosis, biopsy proven minimal change and entire minimal change group (p>0.05) and 0.69 and 0.64 respectively in steroid sensitive and resistant groups (p>0.05). D allele frequency was not significantly different in patients with or without end-stage renal disease (0.64 vs. 0.67 respectively, p>0.005) when 115 patients who were at least five year follow-up were evaluated. The D allele frequency was higher in NS patients than healthy controls and DD or ID genotype was related with frequent relapses. ACE gene I/D polymorphism was not important in laboratory and histological findings and progression of the disease in children with NS.

LOW RENIN-ANGIOTENSIN SYSTEM ACTIVITY GENE POLYMORPHISM AND DYSPLASIA ASSOCIATED WITH POSTERIOR URETHRAL VALVES

Obstructive uropathies, including posterior urethral valves (PUVs) and kidney hypodysplasia, are the most frequent cause of renal failure in children. The role of renin-angiotensin system genes in renal and urinary tract development has been observed in experimental models. The aim of this study was to investigate the distribution of angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin receptor type 1 (ATR1) genetic polymorphisms in children affected by chronic renal failure due to renal hypodysplasia associated with posterior urethral valves or without urethral abnormalities. The study included 50 children (21 with hypodysplasia associated with PUVs, 7 with obstructive uropathy and 22 with pure hypodysplasia) and 50 healthy subjects matched for sex and geographic origin. ACE ID, AGT TC and ATR1 AC gene polymorphisms were assayed in all patients with standard polymerase chain reaction techniques. ACE II was expressed more in patients with PUVs compared to those with other dysplasias and controls (43% vs 7% and 10%, respectively, chi-square test p <0.05), while ATR1 AA was significantly less represented in patients with hypodysplasia compared to controls (38% vs 56%, chi-square test p <0.05). ACE DD and AGT genotypes were not distributed differently in patients with PUVs compared to those with other dysplasias and controls. To our knowledge this is the first report associating severe congenital uropathies and renal hypodysplasia with decreased renin-angiotensin system activity associated with the ACE II genotype and a possible functional imbalance among ATR1 receptors.

Localization of angiotensin converting enzyme by in vitro autoradiography in the rabbit brain

The distribution of angiotensin converting enzyme was examined in the rabbit brain by in vitro autoradiography with the specific radiolabelled inhibitor 125I-351A. In the rabbit, the highest concentrations of radioligand binding were found in the choroid plexus, blood vessels, subfornical organ, vascular organ of the lamina terminalis, area postrema and inferior olive. High levels of binding were found throughout the basal ganglia, consistent with the results in all other species studied. In the midbrain the central gray and the superior colliculus displayed high levels of binding. In the medulla oblongata high levels of binding were associated with the nucleus of the solitary tract and dorsal motor nucleus of vagus, consistent with the pattern in other species. There was moderate labelling throughout both the cerebral and cerebellar cortices, which contrasts to the rat but is consistent with the situation in primates. Angiotensin converting enzyme (ACE) is more widely distributed in rabbit brain that in rat, human and Macaca fascicularis, and the results suggest ACE has a very general role in the metabolism of neuropeptides. Inhibitors of converting enzyme are very widely used in the treatment of hypertension and heart disease, and the rabbit should provide a useful model for examining the effects of these drugs in the brain.

Deletion polymorphism in the gene for angiotensin converting enzyme is associated with elevated fasting blood glucose levels

The frequency and distribution of angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism, and its association with other known risk factors for coronary atherosclerosis, has been studied, in a normal south Italian population. Subjects homozygous for deletion showed elevated fasting blood glucose levels when compared with subjects homozygous for insertion. The difference was consistent with an increased number of type 2 diabetics among the former group of subjects.

A comparison of the properties and enzymatic activities of three angiotensin processing enzymes: Angiotensin converting enzyme, prolyl endopeptidase and neutral endopeptidase 24.11

The discovery of angiotensin-(1–7) [Ang-(1–7)] as a bioactive Ang II fragment of the renin-angiotensin system (RAS) alters the current understanding of the enzymatic components that comprise the RAS cascade. Two neutral endopeptidases, prolyl endopeptidase (E.C. 3.4.21.26) and neutral endopeptidase 24.11 (E.C. 3.424.11), are capable of forming Ang-(1–7) from Ang I and habe been implicated in the in vivo processing of Ang I. This makes them putative Ang processing enzymes and part of the RAS cascade. This review summarizes the physical characteristics and distribution of angiotensin converting enzyme (E.C. 3.4.15.1), a known Ang I processing enzyme, and compares its features to what is known of prolyl endopeptidase and neutral endopeptidase 24.11.

Autoradiographic localization of angiotensin-converting enzyme and angiotensin II binding sites in early atheroma-like lesions in rabbit arteries.

1. Early atheroma-like lesions in rabbits are associated with increased sensitivity to serotonin. The localization and distribution of angiotensin-converting enzyme (ACE) and angiotensin II (AII) binding sites has been studied in these developing lesions by quantitative in vitro autoradiography. 2. In sham-operated control vessels, ACE was localized predominantly to intimal and adventitial sites, whereas in lesioned arteries the level of ACE detected in these regions was significantly reduced. 3. In control vessels AII receptor binding was distributed largely in the outer media, whereas in lesioned vessels AII receptor binding was dispersed throughout the media with the highest levels of binding in the outer media. 4. There was a significant amount of binding associated with ACE and with AII receptors in the extra-adventitial inflammatory tissue of lesioned arteries. 5. Apparent loss of ACE from intimal and adventitial sites may be a consequence of tissue remodelling and cellular proliferation, while the appearance of ACE in abnormal sites could play a role in AII production by the vessel wall. The role of ACE and AII in the developing atheroma-like lesions needs to be investigated further.

Angiotensin converting enzyme in the monkey ( Macaca fascicularis) brain visualized by in vitro autoradiography

Angiotensin converting enzyme is localized in the monkey ( Macaca fascicularis) brain by in vitro autoradiography using the radiolabelled inhibitor, [ 125I]351A. This radioligand binds with high affinity and specificity to monkey cortical sections. Specific inhibitors of converting enzyme, lisinopril and perindoprilat compete for the radioligand binding to monkey cortex sections with inhibitory constants of 10 nM. High concentrations of angiotensin converting enzyme occur in most components of the basal ganglia including the caudate nucleus, putamen, the internal and external globus pallidus, nucleus accumbens, ventral pallidum and the reticular part of the substantia nigra. The distribution of converting enzyme in the caudate nucleus and putamen is heterogeneous, with prominent patches of higher activity. The patches in the caudate nucleus correspond closely with the acetylcholinesterase-poor striosomes. In the hypothalamus, very high levels of angiotensin converting enzyme occur in the median eminence and the pituitary stalk and high concentrations occur in the supraoptic and suprachiasmatic nuclei. Moderate, diffuse binding is observed in the median preoptic nucleus, the medial preoptic area, and in the anterior, lateral, ventromedial, posterior and arcuate nuclei. In the circumventricular organs, the subcommissural and subfornical organs exhibit high levels of angiotensin converting enzyme. The organum vasculosum of the lamina terminalis and the pineal body display moderate enzyme activities whereas the area postrema is devoid of labelling. The interpeduncular nucleus and, in the hippocampal formation, the molecular layer of the dentate gyrus are also intensely labelled. High levels of angiotensin converting enzyme activity are also detected throughout the cerebral cortex with laminations of higher activity corresponding to cell dense layers of the cortex. Layered binding is also present in the cerebellar cortex, with the most intense labelling in the molecular layer. Moderate concentrations of converting enzyme also occur in the paraventricular, medial habenula, lateral habenula and central median nuclei of the thalamus, the amygdala, the central gray, the locus coeruleus, the parabrachial nucleus and dorsal tegmental nucleus. The dorsal vagal complex, inferior olivary nucleus and the caudal subnucleus of the spinal trigeminal nucleus all display high levels of binding. Moderate, diffuse labelling is found throughout the reticular region and is also present in the gracile and cuneate nuclei. Although the overall distribution of angiotensin converting enzyme in the monkey brain resembles that in the rat, there are some striking differences. These include the high levels of binding throughout the monkey cerebral cortex and in the interpeduncular and suprachiasmatic nuclei.

Angiotensin-converting enzyme distribution and hypoxia response in mammal, bird, and fish

Angiotensin I-converting enzyme activity was measured in homogenates of guinea pig ( Cavia porcellus), chicken ( Gallus domesticus), and carp ( Cyprinus carpio) organs. The highest activity was found in guinea pig lung and chicken kidney. In carp the highest activity was found in heart and spleen, although gill arch also showed a high activity. Acute hypoxia decreased the angiotensin I-converting enzyme activity in guinea pig lung and carp gill arch, but the changes in chicken lung and kidney were considered nonsignificant.