sACE Activity Research Articles

Diagnostic efficacy of elevated serum angiotensin-converting enzyme and lymphopenia between presumed sarcoid uveitis and presumed tubercular uveitis.

To evaluate the diagnostic efficacy of elevated serum angiotensin-converting enzyme (sACE) and lymphopenia in presumed sarcoid and tubercular uveitis. A single-centre retrospective study was conducted on a cohort of 755 adult patients with uveitis between January 2019 and June 2020. Demographic, clinical and laboratory data were retrieved from our hospital database. Measurements of serum angiotensin-converting enzyme (sACE) and lymphocyte counts were analysed. The mean age of the patients was 41 ± 13years. Presumed sarcoid uveitis was diagnosed in 50 (7%) patients, presumed tubercular uveitis in 222 (29.4%) and other uveitic entities noted in 483 (64%). Intermediate and posterior uveitis were the most common anatomical diagnosis in presumed sarcoid uveitis (59% and 20%, respectively) and in presumed tubercular uveitis (46% and 38%, respectively). Elevated sACE was noted in 76% of presumed sarcoid uveitis and 46% in presumed tubercular uveitis. The combination of high serum angiotensin-converting enzyme along with lymphopenia was only in 17% in presumed sarcoid uveitis and 9.7% in presumed tubercular uveitis. sACE was found to be a significant risk factor for presumed sarcoid uveitis with an odds ratio of 3.603 (p < 0.002), and in presumed tubercular uveitis odds ratio was not significant with odds ratio of 1.19. Lymphopenia was not found to be a significant factor in both groups. Elevated sACE activity was an independent risk factor for presumed sarcoid uveitis over lymphopenia alone or in combination with lymphopenia.

Soluble Angiotensin Converting Enzyme 2 (ACE2) Is Upregulated and Soluble Endothelial Nitric Oxide Synthase (eNOS) Is Downregulated in COVID-19-induced Acute Respiratory Distress Syndrome (ARDS).

A damaged endothelium is an underlying condition of the many complications of COVID-19 patients. The increased mortality risk associated with diseases that have underlying endothelial dysfunction, such as acute respiratory distress syndrome (ARDS), suggests that endothelial (e) nitric oxide synthase (NOS)-derived nitric oxide could be an important defense mechanism. Additionally, intravenous recombinant angiotensin converting enzyme 2 (ACE2) was recently reported as an effective therapy in severe COVID-19, by blocking viral entry, and thus reducing lung injury. Very few studies exist on the prognostic value of endothelium-related protective molecules in severe COVID-19 disease. To this end, serum levels of eNOS, inducible (i) NOS, adrenomedullin (ADM), soluble (s) ACE2 levels, and serum (s) ACE activity were measured on hospital admission in 89 COVID-19 patients, hospitalized either in a ward or ICU, of whom 68 had ARDS, while 21 did not. In our cohort, the COVID-19-ARDS patients had considerably lower eNOS levels compared to the COVID-19 non-ARDS patients. On the other hand, sACE2 was significantly higher in the ARDS patients. iNOS, ADM and sACE activity did not differ. Our results might support the notion of two distinct defense mechanisms in COVID-19-derived ARDS; eNOS-derived nitric oxide could be one of them, while the dramatic rise in sACE2 may also represent an endogenous mechanism involved in severe COVID-19 complications, such as ARDS. These results could provide insight to therapeutical applications in COVID-19.

Somatic Angiotensin I-Converting Enzyme Regulates Self-Renewal of Mouse Spermatogonial Stem Cells Through the Mitogen-Activated Protein Kinase Signaling Pathway.

Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in the regulation of the renin-angiotensin system. In this study, we used reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis to confirm that somatic ACE (sACE), but not testicular ACE (tACE), is expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. sACE was found to play an important role in SSC self-renewal through the regulation of MAPK-dependent cell proliferation.

Influence of chronic hormone replacement therapy on left ventricular mass and serum-ACE activity

Aims. The aim of this investigation was to study the effects of hormone replacement therapy (HRT) on left ventricular mass (LVM) and serum-angiotensin-converting enzyme (ACE) activity (S-ACE) in well controlled hypertensive postmenopausal women. Methods. In this prospective, randomized, crossover, double-blind trial we studied 20 well controlled hypertensive postmenopausal women who received 6 months of HRT and 6 months of placebo on top of antihypertensive treatment. Two-dimensional M-mode, office blood pressure, 24-h ambulatory blood pressure (ABPM), S-estradiol and S-ACE activity were investigated at baseline, after 6 and 12 months. Results. LVM was significantly influenced by HRT (analysis of variance, ANOVA, p<0.01). However, the order in randomization of HRT and placebo had an impact on the analysis of LVM reduction (baseline – HRT – placebo: ns; baseline – placebo – HRT: p<0.01 ANOVA). Only the women lacking blockade of the renin–angiotensin–aldosterone system (RAAS) as antihypertensive treatment (n=10) experienced a reduction in LVM and a tendency of decreased S-ACE activity in response to HRT compared with baseline (p< 0.05 and p= 0.06 respectively). Conclusions. Six months of HRT resulted in significant reduction of LVM without any change in ABPM. HRT may reduce LVM through interaction with the RAAS, since hypertensive women without RAAS blockade exhibited an effect of HRT on LVM and S-ACE activity, which was not seen in women on RAAS blockade.

Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats

Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

Doseamento das granzimas A e B na sarcoidose pulmonar (estudo experimental)

Sarcoidosis is a systemic disease of unknown aetiology, morphologically characterized by well-formed epithelioid granulomas, which show little or no cen-tral necrosis. These may be present in any organ or tissue. The lung is the most frequently and promi-nently involved target.The granuloma is often very sharply demarcated from the adjacent tissue and is surrounded by a mantle of lymphocytes, which mediate lysis of target cells by various mechanisms, including exocytosis of lytic proteins, perforins and granzymes.Sarcoidosis laboratorial diagnosis is usually made by SACE and Lisozyme dosages. The granzymes A and B could be two other markers of the disease, since the sarcoidosis granuloma is rich in cytotoxic and NK cells.An ELISA Kit was used to measure Granzyme A and B in serum of a normal control group (NC) (n=30), and in two groups with lung pathology: one without sarcoidosis, disease control (DC) (n=21) and other with sarcoidosis (S) (n=11).Our results showed that SACE activity is significantly augmented in S group comparing with NC and DC, respectively: 82,6±32,7/31,9±17,8 - p=0,00017 and 82,6±32,7/31,9±17,8 - p=0,00024. Lisozyme activity is significantly augmented in S and DC groups comparing with NC. Granzyme B showed a significant decrease in DC and S groups comparing with NC. Granzyme A showed a significant decrease between S/NC groups.Our results suggest that the decrease of Granzyme A and B in sarcoidotic patients could be related to an ineffective inflammatory local response related to the formation of sarcoidosis granulomas. More studies are needed, particularly in BAL.Rev Port Pneumol 2005; XI (2): 111-133

Significance of the Interleukin-1 Receptor Antagonist/Interleukin-1β Ratio as a Prognostic Factor in Patients with Pulmonary Sarcoidosis

Background: Various factors such as serum angiotensin-converting enzyme (sACE) activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio, and shadows on chest radiograph have been identified as indexes of disease activity in patients with sarcoidosis. However, it remains to be confirmed whether these factors can predict clinical outcomes. Objective: To examine whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1β ratio can predict the clinical course, we prospectively followed the clinical courses of 30 patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive amounts of IL-1ra or IL-1β in the culture supernatants obtained from BAL fluid macrophages. Methods: Immunoreactive amounts of IL-1ra or IL-1β were measured using ELISA. Changes in pulmonary function, sACE activity, and shadows on chest radiographs during observation periods were evaluated as markers of changes in disease activity. Results: We found that the patients whose shadows on chest radiographs showed improvement had a higher molar IL-1ra/IL-1β ratio than the patients whose shadows persistently remained 4 years after BAL examination (p < 0.05). The molar ratio was found to be positively correlated with improvement of percent vital capacity (p < 0.05) and negatively correlated with the ratio of sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE_LAST/sACE_BAL, p < 0.01). The sACE_LAST/sACE_BAL ratio was significantly lower in patients whose shadows on chest radiographs decreased than in those whose shadows remained unchanged (p < 0.005). Conclusion: The IL-1ra/IL-1β ratio in the BAL fluid macrophage culture supernatants in patients with pulmonary sarcoidosis could be a useful marker in predicting the persistence of granulomatous lesions (chronicity).

Serum angiotensin converting enzyme activity in pulmonary diseases: Correlation with lung function parameters

Serum angiotensin converting enzyme activity (ACE), plasma renin activity (PRA), blood pressure (BP), blood pH, blood gases and lung function parameters were measured in patients with emphysema, extrinsic and intrinsic asthma, malignant pulmonary neoplasms, active sarcoidosis and healthy adults. Serum ACE activity was significantly higher in sarcoidosis (250.22 ± 34.18 U L ); in small cell carcinoma of lung (155.10 ± 38.25 U L ); emphysema (149.82 ± 18.31 U L ); extrinsic asthma (141.22 ± 25.30 U L ) and lower in intrinsic asthma (98.12 ± 15.11 U L ) and squamous cell carcinoma of lung (97.29 ± 18.85 U L ) when compared with that of control subjects (108.20 ± 13.15 U L ). PRA and BP values of the patients with sarcoidosis, emphysema and small cell carcinoma were markedly elevated and sACE activity was found to be correlated with PRA and mean BP in the same diagnostic groups. sACE activity, PRA and BP of smokers were higher than those of non-smokers in control subjects and in patients with emphysema, extrinsic asthma and small cell carcinoma of lung. Oxygen tensions of the patients with emphysema, extrinsic asthma and small cell carcinoma of lung were found to be significantly decreased. Negative correlations between the sACE activity and oxygen tension (r = −0.68) and between the sACE activity and lung function parameters (r = −0.69) were found in these diagnostic groups suggesting that increased sACE level might appeared as a response to chronic hypoxia in the patients with emphysema, extrinsic asthma and small cell carcinoma of lung.

Protruding left ventricular thrombus formation following blunt chest trauma

in the event of myocardial ischemia, SACE increases markedly at maximum effort as well as during recovery. Our data on SACE activity in nonischemic subjects support similar results obtained by Milledge and Catley,” who found SACE to remain unchanged during extended stress testing (up to 60 minutes) in normal healthy subjects. In light of our findings, we propose that SACE elevation could reflect acute endothelial vascular damage (both in general and in particular in the cardiac vasculature) in subjects with clinical and ECG signs of myocardial ischemia during stress testing (regardless of the duration of exercise).

Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54± 16 I.E.) in the upper normal range (controls, 39 ± 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 ± 13, P < 0.001) with persistent proteinuria and with retinopathy (63 ± 14, P < 0.001). A significant correlation was found between proteinuria and S-ACE ( r = 0.98, P < 0.001) and between retinopathy and S-ACE levels ( r = 0.64, P < 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 ± 9 ng/l) and in control (19 ± 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.

Serum Angiotensin-converting Enzyme Is Elevated in Association with Underground Coal Mining

Serum angiotensin-converting enzyme activity (SACE) and lysozyme activity were measured in a group of 40 underground coal miners and two control groups, 20 subjects with sarcoidosis and 15 normal non-dust-exposed volunteers. The miners were grouped first according to whether they had recent exposure (still actively mining or retired three years or less prior to measurement) or temporally more distant exposure (retired more than three years prior to measurement). Secondly, they were grouped as to whether or not they had coal workers' pneumoconiosis (CWP). The subjects with sarcoidosis were grouped according to disease activity. As expected, the subjects with active sarcoidosis had elevated SACE activity compared with normal subjects. The coal miners as a group did not have elevation of their SACE activity. However, the coal miners with recent exposure had elevated SACE activity (57.1 +/- 3.9 U/ml) compared with normal controls (43.8 +/- 1.5 U/ml, p = 0.007). The SACE activity in miners without recent exposure was not elevated (39.8 +/- 1.3 U/ml) compared with the normal controls. No increase in SACE activity was found when the miners were grouped according to the presence or absence of CWP. In contrast, the miners' serum lysozyme activity was not elevated. Since alveolar macrophages are a potential source of SACE, elevation of SACE activity in underground coal miners may reflect alveolar macrophage activation caused by increased pulmonary mixed coal mine dust burden. Furthermore, since both SACE and serum lysozyme are elevated in association with silicosis, these findings may confirm that the macrophage responses to inhaled silica and coal dust differ.

The Circadian Rhythm of Serum Angiotensin-Converting Enzyme Is Disrupted in Ascitic Liver Cirrhosis

An increase in morning fasting levels of plasma (P) renin activity (RA), aldosterone (A) and serum (S) angiotensin-converting enzyme (ACE) activity has been demonstrated in ascitic cirrhotic patients (ACP). Since both PRA and PA change biorhythmically in their time structure, the relationship of SACE activity with the components of the renin-angiotensin-aldosterone system (RAAS) was investigated in clinically healthy subjects (CHS) and ACP. Time-qualified data were chronobiologically analysed by means of the cosinor procedure to resolve and quantify the circadian rhythm (CR). The 24-hour mean levels of PRA, PA and SACE activity were found to be elevated in ACP as compared to CHS. The temporal variability of these analytes was found to be of periodic type along the 24-hour span in CHS, but not in ACP. The well-organized cyclicity in CHS is of relevant interest. PRA and PA cycles were found to phase in a clear antiparallelism with the SACE activity CR. The phase opposition may be, speculatively, related to the physiologic nature of ACE, whose activity is devoted to generate angiotensin II. The disappearance of SACE activity CR in ACP is in accordance with the abolition of PRA and PA cyclicity and suggests a role of liver in regulating the periodic time function of the RAAS and related components.

Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis.

The effect of altered alveolar-capillary permeability on angiotensin converting enzyme (ACE) activity in serum (SACE) was studied in 45 patients with sarcoidosis and 21 healthy controls. In sarcoidosis increased albumin concentrations in the bronchoalveolar lavage fluid (L albumin) and increased ratios of L albumin to albumin in serum (S albumin) indicated an increased permeability of the alveolar-capillary membrane. ACE activity in the lavage fluid (LACE) was correlated with the number of alveolar macrophages in controls, indicating that it may come from these cells. LACE was high in active sarcoidosis while in inactive disease it was similar to that in controls. SACE in sarcoidosis was significantly increased. Ninety per cent of patients with increased L albumin had increased SACE. SACE activity was significantly correlated with concentrations of L albumin and with LACE activity. The relationships between signs of increased membrane permeability and SACE and between LACE and SACE suggest that excess SACE in sarcoidosis may, at least partly, originate in the alveolar space.

The changes of serum-ACE, plasma renin activity and aldosterone in the diabetics with hypertension.

It is well known that the serum-ACE levels are elevated in sarcoidosis, Gaucher’s disease, and some granulomatous diseases. Recently, the serum-ACE level was also found to be elevated in diabetes mellitus. To confirm the possible role of plasma renin activity and aldosterone in the pathogenesis of hypertension and to assess the relationship of serum ACE to the plasma renin activity and aldosterone profiles in diabetics, we measured the levels of serum ACE, plasma renin activity, aldosterone and blood pressure in 38 diabetic patients who were admitted to Kyung Hee University Hospital from June 1981 to September, 1982. The results were as follows: The S-ACE activity was significantly elevated in 38 patients with diabetes mellitus (9.42±6.60 Unit) as compared with that in the healthy controls (2.53±1.54 Unit) (p<0.005) (p<0.005).The S-ACE activity was significantly elevated in 15 hypertensive diabetics (14.29± 7.10 Unit) as compared with that in 23 normotensive diabetics (6.24±3.68 Unit) (p<0.005).The S-ACE activity was elevated in 15 diabetic patients with retinopathy (10.6±4.7 Unit) as compared with the levels in 17 diabetic patients without retinopathy (6.7±4.8 U) (p<0.05).The S-ACE activity was directly correlated to the mean arterial pressure (r=0.54) (p<0.005).The plasma renin activity and aldosternone concentrations in diabetics were not different from the normal controls and had no correlationship to the S-ACE activity.After 2 weeks of insulin therapy in 15 diabetics, the S-ACE activity was not changed.

Determination of serum angiotensin-converting enzyme in sarcoidosis.

Serum angiotensin-converting enzyme activity was measured in 72 patients with sarcoidosis and in 50 normal controls by a radiochemical assay. SACE levels were examined with respect to the 'activity' of the disease, based on clinical, radiographic and physiological assessment. SACE activity in 34 patients with clinical sarcoidosis (147 +/- 44.3 nmol/min/ml) was significantly high (p less than 0.001) when compared to that of 38 patients who had recovered from sarcoidosis (113.9 +/- 26.4 nmol/min/ml) and 50 normal subjects (97.8 +/- 21 nmol/min/ml). SACE levels were significantly different (p less than 0.01) between 15 subjects with 'active' disease (173.9 +/- 51.9 nmol/min/ml) and those with 'inactive' disease (126.1 +/- 26.3 nmol/min/ml). It is concluded that there is a strict correlation between SACE levels and 'activity' of sarcoidosis if multiple criteria (clinical, radiographic and physiological) are employed.