Angiotensin-converting Enzyme Concentration Research Articles

COVID-19 and gastroenterological pathology. Review

SARS‑CoV‑2 has led to numerous cases of coronavirus disease (COVID‑19) around the world. In addition to fever and respiratory symptoms, some COVID‑19 patients also have manifestations from digestive system. On the other hand, patients with chronic diseases of the gastrointestinal tract (GIT) also suffer from coronavirus disease.
 Objective — to provide an understanding of the characteristics, possible mechanisms and consequences of gastrointestinal damage caused by SARS‑CoV‑2 infection, in particular in patients with gastrointestinal tract pathology.
 Literature search was carried out using such databases as Scopus, Web of Science. Clinical studies of patients with COVID‑19 have shown that gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, abdominal pain and diarrhea precede or follow respiratory syndromes with a frequency of about 10 to 60%. Literary sources were studied regarding the relationship of COVID‑19 and such gastroenterological pathologies as gastrointestinal bleeding, hepatitis, pancreatitis and inflammatory bowel diseases. Lesions of the digestive system both in patients without chronic pathology and with existing diseases, apparently, are associated with a high concentration of angiotensin converting enzyme 2 (ACE2) throughout the entire GIT, including the intestine, liver, and pancreas. Some studies have shown that the spike (S) SARS‑CoV‑2 protein has a high affinity for human ACE2, while SARS‑CoV‑2 mainly enters cells through the ACE2 receptor. In addition, endothelial injury and thrombus inflammation and dysregulated immune responses may contribute to extrapulmonary manifestations of COVID 19. This requires an appropriate correction of the diagnostic search and therapy.

Serum Level of Ceruloplasmin, Angiotensin-Converting Enzyme and Transferrin as Markers of Severity in SARS-CoV-2 Infection in Patients with Type 2 Diabetes

The aim of this study was to analyze other possible new markers of severity, at hospital admission, that can be assessed in patients with type 2 diabetes and a SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus infected with the SARS-CoV-2 virus, and 45 healthy persons as controls. The serum level of ceruloplasmin at hospital admission was statistically significant and directly correlated with the severity of COVID-19 (coronavirus disease) (p = 0.037) and with the serum level of IL-6 (interleukin 6) (p = 0.0001). Ceruloplasmin was statistically significant and inversely correlated with the serum iron level (p = 0.0001). However, we observed that ACE (angiotensin-converting enzyme) decreased in severe forms of SARS-CoV-2 infections in patients with type 2 diabetes (p = 0.001). Moreover, the decrease in ACE levels was correlated with an increase in IL-6 levels in these patients (p = 0.001). IL-6 increases were statistically significant and inversely correlated with serum iron, transferrin, and ACE levels. There was a noticed decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p = 0.0001). In addition to the known severity factors in the context of infection with the new coronavirus, increased concentrations of ceruloplasmin and decreased concentrations of ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters, if analyzed upon admission to the hospital, could better inform health professionals about the evolution towards more severe forms of SARS-CoV-2 infections.

Effect of tofacitinib therapy on angiotensin converting enzyme activity in rheumatoid arthritis.

The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) inhibition on RAAS. Here we studied the effects of 12-month tofacitinib treatment on angiotensin converting enzyme (ACE), ACE2 production and ACE/ACE2 ratios in RA along with numerous other biomarkers. Thirty RA patients were treated with tofacitinib in this prospective study. Serum ACE concentrations were assessed by ELISA. ACE2 activity was determined by a specific quenched fluorescent substrate. ACE/ACE2 ratios were calculated. We also determined common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV) by ultrasound. C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were also determined. All measurements were performed at baseline, as well as after 6 and 12 months of tofacitinib treatment. After the dropout of 4 patients, 26 completed the study. Tofacitinib treatment increased ACE levels after 6 and 12 months, while ACE2 activity only transiently increased at 6 months. The ACE/ACE2 ratio increased after 1 year of therapy (p < 0.05). Logistic regression analyses identified correlations between ACE, ACE2 or ACE/ACE2 ratios and RF at various time points. Baseline disease duration also correlated with erythrocyte sedimentation rate (ESR) (p < 0.05). One-year changes of ACE or ACE2 were determined by tofacitinib treatment plus ACPA or RF, respectively (p < 0.05). JAK inhibition increases serum ACE and ACE/ACE2 ratio in RA. Baseline inflammation (ESR), disease duration and ACPA, as well as RF levels at various time points can be coupled to the regulation of ACE/ACE2 ratio. The effect of tofacitinib on RAAS provides a plausible explanation for the cardiovascular effects of JAK inhibition in RA.

The disorders of blood oxygen transport function, hemostasis indicators and endothelium functional state in patients with ruptured arterial aneurysms and the development of delayed cerebral ischemia

Introduction. Rupture of cerebral aneurysms (CA) with the development of intracranial hemorrhage (ICH), complicated in some cases by vascular spasm and delayed cerebral ischemia (DCI), is due to the complex multifactorial genesis of the disease, including changes in the blood oxygen transport function (BOTF), activation of endothelial cells with a release of vasoregulators, reactive oxygen species, inflammatory proteins, as well as disturbances in the hemostasis system.Purpose – to study the indicators of BOTF, primary and secondary hemostasis and the content of some vasoregulatory metabolites in the pre- and postoperative periods in patients with ruptured CA with the development of DCI and without DCI.Materials and methods. The group with DCI included 45 patients; in the group without DCI were 14 people. Clinical-neurological and neuroimaging examinations were carried out, and parameters of BOTF, primary and secondary hemostasis, nitrate/nitrite, angiotensin-converting enzyme (ACE), and PAI-1 concentrations in venous blood were studied before and on days 10–12 after microsurgical clipping of the CA.Results. We diagnosed mild neurological disorders according to the NIHSS scale, confirmed by neuroimaging studies of the brain in the group of DCI patients. It was shown an increase in thrombin-dependent platelet aggregation velocity to 30.6 (24.3; 32.4) AU/min at norm 21.8 (20.3; 24.9) (U, p=0.009) before surgery; and after surgery it was up to 37.4 (30; 44.7) relative to the norm (U, p=0.001). Before surgery, the following was observed: PT shortening to 11.6±0.7 sec at norm 13.2±1.1 (t, p˂0.001), fibrinogen concentration increasing to 4.35 (3.8; 4.8) g/L at norm 3.9 (3.6; 4.1) g/L (U, p = 0.01) and PAI-1 up to 3.9 (2.6; 4.8) ng / mL at norm 2 .7 (2.2; 4.1). After surgery, PT was 11.9±1.1 (t, p˂0.001); fibrinogen - 4.4 (3.9; 4.8) (U, p=0.024), PAI-1 - 4.6 (4.1; 6.7) (U, p=0.0004) respectively. Before surgery, p50 was increased to 28.1 (26.2; 31.6) mm Hg at norm 25.2 (24.3; 26.8) (U, p=0.025); after surgery, it was up to 28.5 (26.8; 30.7) (U, p=0.03) and the ratio of nitrates/nitrites to ACE was reduced to 0.12 (0.08; 0.15) at norm 0.22 (0.15; 0.32) (U, p˂0.001); after - up to 0.11 (0.08; 0.19) (U, p˂0.001) respectively.Conclusion. There has been revealed significant disorders of primary and secondary hemostasis with fibrinolysis inhibition, a decrease in the affinity of hemoglobin to oxygen at the p50 rate and an imbalance of the content of vasoregulatory metabolites in patients with DCI before and after aneurysm clipping, which can be considered as significant factors in the development of DCI after aneurysmal ICH.

Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock

BackgroundSepsis-induced endothelial dysfunction is proposed to cause angiotensin-converting enzyme (ACE) dysfunction and renin–angiotensin–aldosterone system (RAAS) derangement, exacerbating vasodilatory shock and acute kidney injury (AKI). Few studies test this hypothesis directly, including none in children. We measured serum ACE concentrations and activity, and assessed their association with adverse kidney outcomes in pediatric septic shock.MethodsA pilot study of 72 subjects aged 1 week–18 years from an existing multicenter, observational study. Serum ACE concentrations and activity were measured on Day 1; renin + prorenin concentrations were available from a previous study. The associations between individual RAAS components and a composite outcome (Day 1–7 severe persistent AKI, kidney replacement therapy use, or mortality) were assessed.Results50/72 subjects (69%) had undetectable ACE activity (< 2.41 U/L) on Day 1 and 27/72 (38%) developed the composite outcome. Subjects with undetectable ACE activity had higher Day 1 renin + prorenin compared to those with activity (4533 vs. 2227 pg/ml, p = 0.017); ACE concentrations were no different between groups. Children with the composite outcome more commonly had undetectable ACE activity (85% vs. 65%, p = 0.025), and had higher Day 1 renin + prorenin (16,774 pg/ml vs. 3037 pg/ml, p < 0.001) and ACE concentrations (149 vs. 96 pg/ml, p = 0.019). On multivariable regression, increasing ACE concentrations (aOR 1.01, 95%CI 1.002–1.03, p = 0.015) and undetectable ACE activity (aOR 6.6, 95%CI 1.2–36.1, p = 0.031) retained associations with the composite outcome.ConclusionsACE activity is diminished in pediatric septic shock, appears uncoupled from ACE concentrations, and is associated with adverse kidney outcomes. Further study is needed to validate these findings in larger cohorts.

ACE and ACE2 catalytic activity in the fecal content along the gut.

Angiotensin-converting enzyme (ACE) and ACE2 are two major enzymes of the renin-angiotensin-aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1-7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats. Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats. Enzyme activity was evaluated by fluorometric assays using different substrates: Hippuryl-His-Leu for ACE-C-domain, Z-Phe-His-Leu for ACE-N-domain, and Mca-APK(Dnp) for ACE2. ACE and ACE2 concentration was assessed by ELISA. Ratios concerning concentrations and activities were calculated to evaluate the balance of the RAAS. Statistical analysis was performed using Friedman test followed by Dunn's multiple comparisons test or Wilcoxon matched-pairs test whenever needed. ACE and ACE2 are catalytically active in the intestinal content along the rat gut. The ACE N-domain shows higher activity than the C-domain both in the intestinal content and in the intestinal tissue. ACE and ACE2 are globally more active in the intestinal content than in the corresponding intestinal tissue. There was a distal-to-proximal prevalence of ACE2 over ACE in the intestinal tissue. This work is the first to report the presence of catalytically active ACE and ACE2 in the rat intestinal content, supporting future research on the regulatory role of the intestinal RAAS on gut function and a putative link to the microbiome.

Protein nanopore reveals the renin-angiotensin system crosstalk with single-amino-acid resolution.

The discovery of crosstalk effects on the renin-angiotensin system (RAS) is limited by the lack of approaches to quantitatively monitor, in real time, multiple components with subtle differences and short half-lives. Here we report a nanopore framework to quantitatively determine the effect of the hidden crosstalk between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) on RAS. By developing an engineered aerolysin nanopore capable of single-amino-acid resolution, we show that the ACE can be selectively inhibited by ACE2 to prevent cleavage of angiotensin I, even when the concentration of ACE is more than 30-fold higher than that of ACE2. We also show that the activity of ACE2 for cleaving angiotensin peptides is clearly suppressed by the spike protein of SARS-CoV-2. This leads to the relaxation of ACE and the increased probability of accumulation of the principal effector angiotensin II. The spike protein of the SARS-CoV-2 Delta variant is demonstrated to have a much greater impact on the crosstalk than the wild type.

Accelerated ageing and coronary microvascular dysfunction in chronic heart failure in Tgαq*44 mice

Age represents a major risk factor in heart failure (HF). However, the mechanisms linking ageing and HF are not clear. We aimed to identify the functional, morphological and transcriptomic changes that could be attributed to cardiac ageing in a model of slowly progressing HF in Tgαq*44 mice in reference to the cardiac ageing process in FVB mice. In FVB mice, ageing resulted in the impairment of diastolic cardiac function and in basal coronary flow (CF), perivascular and interstitial fibrosis without changes in the cardiac activity of angiotensin-converting enzyme (ACE) or aldosterone plasma concentration. In Tgαq*44 mice, HF progression was featured by the impairment of systolic and diastolic cardiac function and in basal CF that was associated with a distinct rearrangement of the capillary architecture, pronounced perivascular and interstitial fibrosis, progressive activation of cardiac ACE and systemic angiotensin-aldosterone-dependent pathways. Interestingly, cardiac ageing genes and processes were represented in Tgαq*44 mice not only in late but also in early phases of HF, as evidenced by cardiac transcriptome analysis. Thirty-four genes and 8 biological processes, identified as being ageing related, occurred early and persisted along HF progression in Tgαq*44 mice and were mostly associated with extracellular matrix remodelling and fibrosis compatible with perivascular fibrosis resulting in coronary microvascular dysfunction (CMD) in Tgαq*44 mice. In conclusion, accelerated and persistent cardiac ageing contributes to the pathophysiology of chronic HF in Tgαq*44 mice. In particular, prominent perivascular fibrosis of microcirculation resulting in CMD represents an accelerated cardiac ageing phenotype that requires targeted treatment in chronic HF.

Enalaprilat as a new means of preventing the development of retinopathy of prematurity.

In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina were investigated. The study was performed on 136 newborn Wistar rat pups divided into 2 groups: group A - experimental (animals with ROP, n=64) and group B - control (n=72). Each group was further divided into 2 subgroups: A0 and B0 (n=32 and n=36, respectively) - animals that did not receive injections of enalaprilat, and A1 and B1 (n=32 and n=36, respectively) - animals treated with daily intraperitoneal (i.p.) injections of enalaprilat (0.6 mg/kg of body weight). This treatment started on day 2 and lasted either to day 7 or to day 14 in accordance with the therapeutic scheme. Animals were taken out of the experiment on day 7 and day 14. In samples of the vitreous body and retina, the content of ACE and AT-II was determined by enzyme immunoassay. On day 7 in subgroups A1 and B1 the levels of ACE and AT-II in the vitreous did not differ, while on day 14 were lower than in subgroups A0 and B0, respectively. Changes in the parameters studied in the retina were somewhat different from those found in the vitreous body. On the seventh day, the level of ACE in the retina of animals of subgroup B1 did not differ significantly from subgroup B0, and in subgroup A1 it was increased compared to subgroup A0. On day 14, its significant decrease was noted in subgroups A1 and B1 as compared with subgroups A0 and B0. At the same time, the level of AT-II in the retina of rat pups of subgroup B1 was lower than in subgroup B0, both on day 7 and day 14. On day 7, the concentration of AT-II, as well as the concentration of ACE, increased in subgroup A1 as compared to subgroup A0. On day 14, this parameter in subgroup A1 was significantly lower as compared to subgroup A0, but significantly higher than in subgroup B1. It should be noted that i.p. injections of enalaprilat, increased a death rate of animals of both groups. The use of enalaprilat, starting from the preclinical period of the ROP development, led to a decrease in the activity of the renin-angiotensin system (RAS) in ROP animals at the onset of retinopathy in the experimental model used. This opens up prospects for considering enalaprilat as a means of preventing the development of this pathology; however, the recognized high toxicity of the drug requires further studies and correction of the timing of its administration and dosage in order to achieve a balance of efficacy and safety of use in order to prevent the development of ROP in children.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Renin-angiotensin system in the central nervous system: focus on Huntington's disease.

Peptidomic analysis of the angiotensin-converting-enzyme inhibitory peptides in milk fermented with Lactobacillus delbrueckii QS306 after ultrahigh pressure treatment

In this study, we assessed the effect of ultrahigh pressure (UHP) treatment on the concentration of peptides and angiotensin-converting enzyme (ACE) inhibitory activity in milk fermented with Lactobacillus delbrueckii QS306. The peptides were identified using peptidomic analysis, and 313 unique peptides were identified. These peptides were derived from 53 precursor proteins. Before and after UHP treatment, 361 (22.2%) peptide sequences exhibited difference, and 53 peptide segments were significantly different. Among them, small peptides (amino acid residues ≤6) isoelectric were point at pH 5–6, and the net charge was mainly positive or neutral. With hydrophobicity and ACE inhibitory activity as screening indicators, 214 small peptides with potential ACE inhibitory activity were identified, and 130 new peptides had potential ACE inhibitory activity. A novel ACE inhibitory peptide VAPFP was synthesized, whose in vitro inhibition rate was 10.56 μmol\\/L. Therefore, using peptidomics, the changes in peptide sequences and enhancement in ACE inhibitory activity before and after UHP treatment could be effectively identified in milk fermented with Lactobacillus delbrueckii QS306. This study provided a convenient method for the discovery and identification of new ACE inhibitory peptides.

493 A CASE REPORT OF SUBACUTE INFLAMMATORY HEART DISEASE WITH AN ATYPICAL ONSET

Abstract Background Inflammatory heart disease is a heterogeneous process with variegate clinical manifestations. The acute phase is characterized by a sudden injury involving cardiomyocytes, cardiac conduction system and/or pericardium, with different pathophysiological implications. Case Summary A 26-year-old previously healthy woman presented for worsening fatigue and bradycardia. The ECG at admission showed total heart block with infra-Hisian escape rhythm, heart rate was 36 bpm. She reported no history of tick bite or recent inflammatory event; body temperature was 36,8 °C. Laboratory assessment showed persistently raised troponin (28943 -&amp;gt; 32632 ng/l), C-reactive protein was 0,70 mg/l, white blood cells 4,86×10^3/µl, procalcitonin 0,03 µg/l, interleukin-6 was 60,5 pg/ml (n.v. &amp;lt;28,0) and NT-pro-BNP was 312 pg/ml. Borrelia, Salmonella, Ricketsiae, Toxoplasma screening was negative for acute infection as well as any other viral serology. Comprehensive laboratory autoimmunity assessment was negative. Echocardiography revealed normal biventricular volume and kinetics, no valvulopathies and no pericardial effusion. Coronary angiogram was normal. The cardiac magnetic resonance showed extensive oedema and contextual late gadolinium enhancement predominantly in the interventricular septum and mid segment of the anterior wall. Serum angiotensin-converting enzyme concentration was normal. Due to persistent heart block, after 5 days the patient underwent endomyocardial biopsy that showed slight oedema and mild fibrosis without lymphocytic infiltration nor histochemical findings suggestive of active myocarditis. Granulomas were absent. Viral analysis on myocardium was negative. An intermediate dose of steroids was started with a progressive restoration of 1:1 atrioventricular conduction and shortening of QRS up to incomplete right bundle branch block, hence the patient was discharged without pacemaker implantation. Discussion In heart inflammatory diseases with bradyarrhythmic onset, atrioventricular conduction may be restored with targeted therapy. Multimodality assessment is crucial in the diagnostic and therapeutic work-up of these cases.

In Vivo Antihypertensive Activity and UHPLC-Orbitrap-HRMS Profiling of Cuphea ignea A. DC.

Cuphea ignea A. DC. is an ornamental tropical plant belonging to the family Lythraceae. The aim of this study is to verify the in vivo antihypertensive potential of C. ignea A. DC. and to explore its metabolic profile using a UHPLC-Orbitrap-HRMS technique. The results revealed that the ethanolic extract of the leaves in two doses (250 and 500 mg/kg b.wt.) significantly normalized the elevated systolic blood pressure in N(G)-nitro-l-arginine-methyl ester-induced hypertension in rats. An angiotensin-converting enzyme (ACE) concentration was significantly decreased by the high dose extract compared to lisinopril. Nitric oxide (NO) level was significantly restored by both doses. Concerning the oxidative stress parameters, both doses displayed significant reduction in malondialdehyde (MDA) level while the high dose restored elevated glutathione level. These biochemical results were clearly supported by the histopathological examination of the isolated heart and aorta. A UHPLC-Orbitrap-HRMS study was represented by a detailed metabolic profile of leaves and flowers of C. ignea A. DC., where 53 compounds were identified among which flavonoids, fatty acids, and hydrolysable tannins were the major identified classes. This study established scientific evidence for the use of C. ignea A. DC., a member of genus Cuphea as a complementary treatment in the management of hypertension.

The systemic renin-angiotensin system in COVID-19

SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the “alternative” (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1–7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I–II) and alt-RAS (angiotensins 1–7 and 1–5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1–6: 0.12; days 11–16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Investigation of Serum Angiotensin-Converting Enzyme (ACE) Concentration and ACE Gene Polymorphism in Patients With SARS-CoV-2 Pneumonia Admitted to the Emergency Department.

Background This study seeks to investigate the distribution of the angiotensin-converting enzyme (ACE) gene polymorphism and serum levels in patients with viral pneumonia and predict which polymorphism will lead to severe progression of the disease. Methodology The serum ACE levels and ACE gene polymorphisms were successfully evaluated with respect to subsequent viral pneumonia using records of 100 patients with viral pneumonia and 100 healthy controls. Results ACE serum concentration was statistically significantly elevated. ACE serum concentration with a cut-off value of ≥5,256.05 pg/mL had 85.3% sensitivity and 83.2% selectivity. In addition, patients with ACE genotype D/D were 0.08 times more likely to manifest severe lung involvement than those with I/I, and patients with the I/D genotype were 0.02 times more likely than their counterparts with I/I. The computed tomography findings of the patients revealed that ACE serum concentration was significantly effective in discriminating between mild and moderate-to-severe lung involvement. No significant difference was observed between the blood parameters and ACE genotype distributions. Conclusions I/D polymorphism likely affects the expression of the ACE gene and/or the function of the angiotensin I converting enzyme. The D/D genotype is associated with vessel wall thickness and higher blood pressure. Strong evidence was found between D/D and I/D genotypes in the patient cohort concerning genotypes and ACE serum concentration. Further analysis showed that ACE serum levels were more elevated in the D/D genotype compared to the I/D genotype in the patient cohort.

Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes.

ContextThe plasma concentrations of angiotensin-converting enzyme 2 ([pACE2) has been independently associated with cardiovascular diseases.ObjectiveHigher [pACE2] concentrations could be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events.MethodsUsing an inception observational cohort, we examined [pACE2] among 168 incident patients with PA. The expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells (PBMCs).ResultsIncident PA and EH patients had similarly elevated [pACE2] (47.04 ± 22.06 vs. 46.73 ± 21.06 ng/ml, p= 0.937). Age was negatively (β, -2.15, p= 0.033) and higher serum potassium level (β, 2.29, p= 0.024) was positively correlated with higher [pACE2] in PA patients. Clinical complete hypertension-remission after adrenalectomy (PASO criteria) was achieved in 36 (50%) of the 72 surgically-treated uPA patients. At follow-up, the [pACE2] decreased in surgically-treated patients who had (p< 0.001) or had no (p= 0.006) hypertension-remission, but the [pACE2] attenuation was not significant in uPA (p= 0.085) and biPA (p= 0.409) administered with minerocorticoid receptor antagonist (MRA). Persistently elevated [pACE2] (> 23ng/ml) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (HR, 8.8, p = 0.04); with a mean followed up of 3.29 years. TMPRSS2 mRNA expression was higher in uPA (p= 0.018) and EH (p= 0.038) patients than that in normotensive controls; it was also decreased after adrenalectomy (p< 0.001).ConclusionsPA and EH patients had elevated [pACE2] and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated [pACE2] (> 23ng/ml) after targeted treatments was associated the risk of mortality and incident cardiovascular events.

The Influence of SARS-CoV-2 Infection on Lipid Metabolism-The Potential Use of Lipid-Lowering Agents in COVID-19 Management.

Several studies have indicated lipid metabolism alterations during COVID-19 infection, specifically a decrease in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations and an increase in triglyceride (TG) levels during the infection. However, a decline in triglycerides can also be observed in critical cases. A direct correlation can be observed between a decrease in serum cholesterol, HDL-C, LDL-C and TGs, and the severity of the disease; these laboratory findings can serve as potential markers for patient outcomes. The transmission of coronavirus increases proportionally with rising levels of cholesterol in the cell membrane. This is due to the fact that cholesterol increases the number of viral entry spots and the concentration of angiotensin-converting enzyme 2 (ACE2) receptor, crucial for viral penetration. Studies have found that lower HDL-C levels correspond with a higher susceptibility to SARS-CoV-2 infection and infections in general, while higher HDL-C levels were related to a lower risk of developing them. However, extremely high HDL-C levels in serum increase the risk of infectious diseases and is associated with a higher risk of cardiovascular events. Low HDL-C levels are already accepted as a marker for risk stratification in critical illnesses, and higher HDL-C levels prior to the infection is associated with a lower risk of death in older patients. The correlation between LDL-C levels and disease severity is still unclear. However, TG levels were significantly higher in non-surviving severe patients compared to those that survived; therefore, elevated TG-C levels in COVID-19 patients may be considered an indicator of uncontrolled inflammation and an increased risk of death.

Correlation between serum angiotensin-converting enzyme (ACE) levels and intervertebral disc degeneration

Studies have shown that the renin-angiotensin system (RAS) might play an essential role in intervertebral disc degeneration (IDD). The study aimed to investigate the relationship between serum angiotensin-converting enzyme (ACE) concentration and IDD and its predictive value for severe disc degeneration. 245 patients who came to our hospital for low back pain were recruited, and blood samples were collected for routine examination. Descriptive data and demographic parameters were collected. The cumulative grade 1 was calculated by summing up the Pfirrmann grade of all lumbar discs. ACE concentration grouping was determined via tertile split. Correlation analysis and multivariable linear regression analysis were performed to determine the relationship between ACE and IDD. The receiver's degree of disc degeneration (ROC) curve determined the ACE's predictive value. Results indicated that there was no significant difference in demographic parameters among groups. Correlation analysis and multivariate linear analysis showed that ACE was an independent risk factor for IDD. The cumulative grade 1 increased significantly with the increase in ACE concentration, which was consistent with the correlation analysis. Average Pfirrmann grade < 4 indicates mild to moderate degeneration, and grade ≥ 4 indicates severe degeneration in terms of an individual disc. From L1/2 to L5/S1, the mean plasma ACE concentration was significantly higher in the severe degeneration group than in the mild to moderate degeneration group. According to the ROC curve, the cut-off value of ACE levels was 22.5. patients with ACE > 22.5 had severe degeneration. The sensitivity and specificity were 0.762 and 0.521, respectively.

Determination of angiotensin-converting enzyme concentration in cardiovascular patients

Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year, More than four out of five CVD deaths are due to heart attacks and strokes, and one third of these deaths occur prematurely in people under 70 years of age . The circulating Renin Angiotensin Aldosterone system (RAAS) comprises liver - secreted angiotensinogen (AGT) that is enzymatically converted into angiotensin I (Ang I). ACE, as a key component in RAS, converts angiotensin I to angiotensin II, Angiotensin II increase the production of adhesion molecules and chemokines stimulates LDL oxidation and foam cell formation in macrophages, Increased level of the ACE and subsequent ACE activity by raising the production of angiotensin II can lead to atherosclerosis . A number of 100 subjects were involved in this investigation, 100 patients of CVDs in AL-Saddir Hospital and AL Hkem Hospital, in AL- Najaf province, 70 of them with CVDs and the other 30 healthy individuals, were used as control.The study was conducted to find out the importance of Determination of angiotensin-converting enzyme concentration in cardiovascular patients and some clinical and biochemical variables .

Importance of the Precautionary Principle With Regard to the Risk of Exposure to Aerosols Containing Viral Loads of SARS-CoV-2 Present in Feces: In Perspective.

In COVID-19 infection, the emissions of droplets and aerosols produced by the respiratory tract of contaminated subjects may represent a high risk of spreading the SARS-COV-2 virus in the environment. Thus, studies have shown that there is, at least, another source of droplets and aerosols in which viral particles of SARS-COV-2 can be found. It happens after flushing of toilet to dispose of the stools of a patient who has contracted COVID-19. The presence of viral particles of SARS-COV-2 in the stool could be linked to the concentration of angiotensin-converting enzyme 2 (ACE2) found on the surface of intestinal cells. Therefore, there is a reason to wonder whether the emission of viral particles by activating a toilet flush could represent an important potential risk of contamination for health care workers. To investigate this hypothesis, we have correlated different studies on the production of droplets and aerosols as well as the presence of viral particles following flush of toilet. This pooling of these studies led to the following conclusion: the precautionary principle should be applied with regard to the potential risk represented by viral particles of SARV-COV-2 in the stool when flushing the toilet.