Plasma Angiotensin-converting Enzyme Research Articles

Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)

IntroductionACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1–7) causing vasodilatation...

Long-term intake of corn gluten meal protein hydrolysate attenuated hypertension development and modulated associated plasma metabolite levels in spontaneously hypertensive rats

This study evaluated the long-term antihypertensive effect of corn gluten meal protein hydrolysate (CGM-H) on spontaneously hypertensive rats (SHRs). Plausible pathways governing blood pressure were also evaluated based on untargeted metabolomic analysis. The casein diet containing 1 % of CGM-H and peptides obtained from ultrafiltration membranes attenuated the development of hypertension in SHRs after a 6-week oral administration with similar efficacy, while the control group showed progressive hypertension. Plasma renin and angiotensin converting enzyme (ACE) activity and total peroxides level of the corn peptides-treated groups decreased when compared with the control (p < 0.05). In addition, the corn peptides up-regulated antihypertensive metabolites such as prostaglandin K2 and 11-ketotestosterone, while corticosterone, biotin, and plasma fatty acids were down-regulated. This study demonstrates that corn peptides did not only inhibit ACE and renin activities, but also modulated the biosynthesis and metabolisms of fatty acids, sex hormones, and aldosterone, which would have contributed to attenuation of hypertension.

Hemp seed protein and its hydrolysate compared with casein protein consumption in adults with hypertension: a double-blind crossover study

BackgroundThe effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans. ObjectivesWe aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein. MethodsIn a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures. ResultsCompared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein. ConclusionsThese results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension.This trial was registered at clinicaltrials.gov as NCT03508895.

Haematological Profile and ACE2 Levels of COVID-19 Patients in a Metropolis in Ghana

Background: Several studies have linked coronavirus disease 2019 (COVID-19) risk to age and ABO blood groups. Variations in plasma angiotensin-converting enzyme 2 (ACE2) levels and blood counts have been reported, suggesting an association between disease severity and low lymphocyte levels. Aim: this study aimed to understand how these factors relate to COVID-19 in Ghanaian patients, considering geographical and demographic differences. Methods: Participants were recruited from six hospitals in Kumasi, Ghana, between June 2020 and July 2021. Nasopharyngeal swabs were taken to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and blood samples were collected for complete blood count testing, ABO/Rhesus typing, and assessment of plasma ACE2 levels. Demographic and COVID-19 severity data were gathered, and IBM SPSS version 25.0 was used for analysis. Results: Overall, 515 patients were enrolled, out of which 55.9% (n = 288/515) were males and 50.3% (n = 259/515) tested positive for SARS-CoV-2. The median age was 37 years (IQR = 26–53). Age was significantly associated with SARS-CoV-2 infection (p = 0.002). The severe COVID-19 group was the oldest (70 years, IQR = 35–80) and presented with anaemia (haemoglobin, g/dL: 9.55, IQR = 7.85–11.93), leukocytosis (WBC × 103/μL: 15.87, IQR = 6.68–19.80), neutrophilia (NEUT × 106/μL: 14.69, IQR = 5.70–18.96) and lymphocytopenia (LYMPH × 106/μL: 0.47, IQR = 0.22–0.66). No association was found between SARS-CoV-2 positivity and ABO (p = 0.711) or Rh (p = 0.805) blood groups; no association was also found between plasma ACE2 levels and SARS-CoV-2 status (p = 0.079). However, among COVID-19 participants, plasma ACE2 levels were significantly reduced in the moderate illness group (40.68 ng/mL, IQR = 34.09–48.10) compared with the asymptomatic group (50.61 ng/mL, IQR = 43.90–58.61, p = 0.015). Conclusions: While there may be no real association between the ABO blood group, as well as plasma ACE2 levels, and SARS-CoV-2 infection in Ghanaian patients, older individuals are at a higher risk of severe disease. Anaemia, and leukocytosis with lymphocytopenia may be indicators of poor disease progression.

Blood ACE Phenotyping for Personalized Medicine: Revelation of Patients with Conformationally Altered ACE.

Background: The angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated blood ACE is a marker for granulomatous diseases and elevated ACE expression in tissues is associated with increased risk of cardiovascular diseases. Objective and Methodology: We applied a novel approach -ACE phenotyping-to find a reason for conformationally impaired ACE in the blood of one particular donor. Similar conformationally altered ACEs were detected previously in 2-4% of the healthy population and in up to 20% of patients with uremia, and were characterized by significant increase in the rate of angiotensin I hydrolysis. Principal findings: This donor has (1) significantly increased level of endogenous ACE inhibitor in plasma with MW less than 1000; (2) increased activity toward angiotensin I; (3) M71V mutation in ABCG2 (membrane transporter for more than 200 compounds, including bilirubin). We hypothesize that this patient may also have the decreased level of free bilirubin in plasma, which normally binds to the N domain of ACE. Analysis of the local conformation of ACE in plasma of patients with Gilbert and Crigler-Najjar syndromes allowed us to speculate that binding of mAbs 1G12 and 6A12 to plasma ACE could be a natural sensor for estimation of free bilirubin level in plasma. Totally, 235 human plasma/sera samples were screened for conformational changes in soluble ACE. Conclusions/Significance: ACE phenotyping of plasma samples allows us to identify individuals with conformationally altered ACE. This type of screening has clinical significance because this conformationally altered ACE could not only result in the enhancement of the level of angiotensin II but could also serve as an indicator of free bilirubin levels.

The role of plasma angiotensin-converting enzyme and interleukin-6 levels on the prognosis of non-dialysis chronic kidney disease patients

Context: Inflammatory factors and oxidative stress were discovered to play significant roles in the progression of chronic kidney disease (CKD). There is, however, no research on the direct impact of high plasma angiotensin converting enzyme (ACE) and interleukin (IL)-6 levels on CKD prognosis, particularly in non-hemodialysis patients. Aims: To investigate the potential role of plasma ACE and IL-6 levels in CKD prognosis. Methods: A total of 75 non-dialysis CKD patients participated in this cross-sectional study. The estimated glomerular filtration rate (e-GFR) and albuminuria were used to determine the prognosis of CKD. The plasma ACE and IL-6 levels were measured using an enzyme-linked immunoassay (ELISA). Spearman's rank correlational analysis was used to examine the relationship between ACE and IL-6 plasma levels with the prognosis of CKD. Results: The result showed a statistically significant correlation between age and plasma ACE (p = 0.038, r = 0.241), serum creatinine, and urine albumin-creatinine ratio with CKD prognosis (p&lt;0.0001). A negative significant correlation was found between the e-GFR and CKD prognosis (p&lt;0.0001). Additionally, there were also significant correlations between plasma ACE and IL-6 with CKD prognosis (p = 0.021, r = 0.266 and p = 0.04, r = 0.238, respectively). A significant positive correlation was also found between plasma ACE and IL-6 (p = 0.024, r = 0.260). Conclusions: There was a significant correlation between plasma ACE and IL-6 levels with CKD prognosis. Further investigation revealed a statistically significant positive relationship between plasma ACE and IL-6 levels.

Angiotensin-converting enzyme 2 in human plasma and lung tissue

Purpose We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery. Materials and methods The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women). Results In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20). Conclusion ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.

Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial.

Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations. Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO3) or ACE inhibitor (ACEi: enalapril) for 8weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention. Forty-eight participants (nACEi = 23, nPLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACEi (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus. Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.

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.

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Basal VEGF-A and ACE Plasma Levels of Metastatic Colorectal Cancer Patients Have Prognostic Value for First-Line Treatment with Chemotherapy Plus Bevacizumab.

Simple SummaryMolecular biology knowledge has enabled the incorporation of targeted therapies, such as the anti-angiogenic drug bevacizumab, into combined chemotherapy regimens for the treatment of metastatic colorectal cancer. However, to date, there are no reliable useful biomarkers to predict the efficacy of this anti-angiogenic therapy. The objective of this prospective study was to evaluate potential circulating plasma biomarkers in mCRC patients prior to the start of first-line treatment with chemotherapy plus bevacizumab. We found that high VEGF-A and low ACE plasma levels were associated with poor OS after treatment. Moreover, a simple scoring system combining both biomarkers efficiently stratified patients into high- or low-risk groups, which allows the selection of patients for anti-angiogenic therapy.The identification of factors that respond to anti-angiogenic therapy would represent a significant advance in the therapeutic management of metastatic-colorectal-cancer (mCRC) patients. We previously reported the relevance of VEGF-A and some components of the renin–angiotensin-aldosterone system (RAAS) in the response to anti-angiogenic therapy in cancer patients. Therefore, this prospective study aims to evaluate the prognostic value of basal plasma levels of VEGF-A and angiotensin-converting enzyme (ACE) in 73 mCRC patients who were to receive bevacizumab-based therapies as a first-line treatment. We found that high basal VEGF-A plasma levels were significantly associated with worse overall survival (OS) and progression-free survival (FPS). On the other hand, low ACE levels were significantly associated with poor OS. Importantly, a simple scoring system combining the basal plasma levels of VEGF-A and ACE efficiently stratified mCRC patients, according to OS, into high-risk or low-risk groups, prior to their treatment with bevacizumab. In conclusion, our study supports that VEGF-A and ACE may be potential biomarkers for selecting those mCRC patients who will most benefit from receiving chemotherapy plus bevacizumab treatment in first-line therapy. Additionally, our data reinforce the notion of a close association between the RAAS and the anti-angiogenic response in cancer.

The effect of purple-black barberry (Berberis integerrima) on blood pressure in subjects with cardiovascular risk factors: a randomized controlled trial

Ethnopharmacological relevanceBerberis integerrima commonly known as “barberry” belongs to the Berberidaceae family and has been used as a medicinal plant in Iranian traditional medicine. Aim of the studyOur aim in this study was to investigate the effects of barberry consumption on blood pressure (BP). Materials and methodsEighty-four medicated hypertensive patients were selected and randomly allocated to barberry and placebo groups. The barberry group received 10 g/day dried purple-black barberry powder, once daily, for 2-months. Systolic, diastolic, and mean arterial BP was assessed through 24-h ambulatory BP monitoring before and after 2-month treatment. The estimation of sodium and potassium intake was done through measurement of sodium and potassium in 24-h urinary samples. Plasma and urinary nitrite, and nitrate (NOx) levels, as well as plasma angiotensin-converting enzyme (ACE) activity, were also determined. ResultsSeventy-eight participants with an average age of 54.12 ± 10.32 years and BMI of 27.93 ± 2.22 kg/m2 completed the study. There was no significant difference in body weight, physical activity, and the 24-h urinary sodium and potassium excretion between the two groups before and after the study. After adjusting for baseline values and changes in sodium intake, systolic, and mean arterial BP decreased significantly in the barberry group compared to the placebo group (p = 0.015 and p = 0.008, respectively). Plasma NOx levels and ACE activity were not different between the two groups, but urinary NOx was increased significantly in the barberry group compared to the placebo group (p = 0.008). ConclusionsIn patients treated with antihypertensive drugs, daily consumption of purple-black barberry can be effective in improving systolic BP control.

Reduced blood pressure in sickle cell disease is associated with decreased angiotensin converting enzyme (ACE) activity and is not modulated by ACE inhibition.

BackgroundSickle cell disease (SCD) incurs vaso-occlusive episodes and organ damage, including nephropathy. Despite displaying characteristics of vascular dysfunction, SCD patients tend to present relatively lower systemic blood pressure (BP), via an unknown mechanism. We investigated associations between BP and renin-angiotensin-system (RAS) components in SCD and determined whether an inhibitor of angiotensin converting enzyme (ACE; often used to slow SCD glomerulopathy) further modulates BP and RAS components in a murine model of SCD.MethodsBP was compared in human subjects and mice with/without SCD. Plasma angiotensin II, ACE and renin were measured by immunoassay. BP was reevaluated after treating mice with enalapril (25 mg/kg, 5x/week) for 5 weeks; plasma and organs were stored for angiotensin II and ACE activity measurement, and quantitative real-time PCR.ResultsDiastolic BP and systolic BP were significantly lower in patients and mice with SCD, respectively, compared to controls. Reduced BP was associated with increased plasma renin and markers of kidney damage (mice) in SCD, as well as significantly decreased plasma ACE concentrations and ACE enzyme activity. As expected, enalapril administration lowered BP, plasma angiotensin II and organ ACE activity in control mice. In contrast, enalapril did not further reduce BP or organ ACE activity in SCD mice; however, plasma angiotensin II and renin levels were found to be significantly higher in enalapril-treated SCD mice than those of treated control mice.ConclusionRelative hypotension was confirmed in a murine model of SCD, in association with decreased ACE concentrations in both human and murine disease. Given that ACE inhibition has an accepted role in decreasing BP, further studies should investigate mechanisms by which ACE depletion, via both Ang II-dependent and alternative pathways, could contribute to reduce BP in SCD and understand how ACE inhibition confers Ang II-independent benefits on kidney function in SCD.

Comparison of patient characteristics between East Asian and non-East Asian patients with insulin autoimmune syndrome.

Insulin autoimmune syndrome (IAS) is the third most common cause of spontaneous hypoglycaemia in Japan but very rare in the rest of the world. We aimed to identify factors, which are associated with the occurrence of IAS and which may differ between East Asian and non-East Asian patients. A PubMed search using the search terms 'insulin autoimmune syndrome' and 'Hirata disease' revealed a total of 287 reports of IAS cases, including one previously unpublished own case. Mean age (±standard deviation) was 52 ± 19 years in East Asian and 54 ± 21 years in non-East Asian patients (p > .05). In both groups, there were more females. Mean body mass index was lower in East Asian than in non-East Asian patients (23.0 ± 4.3 vs. 27.1 ± 5.6 kg/m2 , p < .0001). Postprandial hypoglycaemia was more common in non-East Asian patients (p < .05). East Asian patients took more frequently antithyroid medications and non-East Asian patients angiotensin-converting enzyme (ACE) inhibitors (both p < .0001). Graves' disease and other autoimmune diseases were more frequently observed in East Asian patients (both p < .01). Parameters of glucose metabolism were comparable in both groups, independent of diabetes diagnosis (p > .05), except for insulin that was higher in East Asian compared to non-East Asian metabolically healthy patients (p < .01). Human leukocyte antigen (HLA)-DRB1*0406 was the most frequent HLA-type in East Asian patients (p < .0001), whereas DRB1*0403 and *0404 were more frequent in non-East Asian patients (both p < .05). Non-East Asian patients received more secondary treatments, including plasmapheresis and rituximab, whereas medication discontinuation was more common in East Asian patients (all p < .05). Outcome was similar in both groups (p > .05). Factors associated with IAS markedly differ between East Asian and non-East Asian patients, with autoimmune disorders, particularly Graves' disease, antithyroid medications, and HLA-DRB1*0406 more prevalent in East Asian patients and cardiovascular and plasma cell diseases, ACE inhibitors and HLA-DRB1*0403 more prevalent in non-East Asian patients.

Combined antihypertensive effect of unripe Rubus coreanus Miq. and Dendropanax morbiferus H. L\xe9v. Extracts in 1 kidney-1 clip hypertensive rats and spontaneously hypertensive rats

BackgroundWe previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. Lév. leaf (Hy-DP) and unripe Rubus coreanus Miq. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; however, their combined effect on antihypertensive activity has not been explored.MethodsThe present study aims to investigate the effect of a chronic optimized mixture (HDR-2, composed of Hy-DP and 5-uRCK in a 2:1 mass ratio) on vascular tension and blood pressure in two different hypertensive rat models.ResultsThe results showed that HDR-2 concentration-dependently relaxed endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine. Antihypertensive effects were assessed in vivo on a 1 kidney-1 clip (1 K-1C) rat model of hypertension and spontaneously hypertensive rats (SHRs). Acute HDR-2 treatment significantly decreased systolic blood pressure (SBP) 3 h posttreatment in both models. Chronic HDR-2 administration also significantly decreased SBP in the hypertensive rat models. Moreover, HDR-2 increased eNOS protein expression and phosphorylation levels in the aorta.ConclusionChronic HDR-2 administration may effectively improve vascular function by decreasing plasma angiotensin-converting enzyme (ACE) activity and AngII levels. HDR-2 significantly improved acetylcholine (ACh)-induced aortic endothelium-dependent relaxation and affected sodium nitroprusside (SNP)-induced endothelium-independent relaxation in SHRs.

T Cell-based RAS Activity and Insulin Levels in Obese Subjects with Low Grade Inflammation

BackgroundObesity is a major contributor to inflammation and oxidative stress that are key underlying causes for insulin resistance (IR) and diabetes. Accumulated evidence suggest that RAS may serve as a strong link between IR and obesity. We investigated RAS activity in circulating T cells by obese subjects with and without angiotensin (Ang) II stimulation in presence or not of IR and of low-grade inflammation. MethodsWe studied 29 obese and 10 healthy subjects. After T-lymphocytes isolation, mRNAs for angiotensin converting enzyme (ACE) and angiotensin 1-receptor (AT1-R) were quantified by reverse transcription polymerase chain reaction (RT-PCR). High-sensitivity C-reactive protein (hs-CRP), insulin and inflammatory cytokines serum levels, plasma renin activity (PRA) and ACE activity in cell pellet and supernatant, and angiotensin (Ang) II T cell content were also measured. ResultsUnder baseline conditions, RAS gene expressions, ACE activity and Ang II levels in T cells, but not PRA, of obese subjects with or without IR and with or without hs-CRP ≥3mg/dl were higher than in controls (p < 0.05). The increase in all parameters induced by Ang II was significantly higher in T cells from the obese subjects with hs-CRP ≥3 mg/dl than in controls or in the obese subjects with hs-CRP <3 mg/dl. In the obese subjects with low grade inflammation and IR, the cytokine serum levels and T cells RAS gene expression was inversely correlated with insulin serum concentration. ConclusionsLow grade inflammation amplifies the T cell RAS response to Ang II stimulation. T cell RAS gene expressions and serum levels of inflammatory cytokines were inversely related with insulin serum concentration. A protective role of insulin towards the development of inflammatory events can be hypothesized.

Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population.

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A Comprehensive Study on Anti-hypertensive properties of Punica granatum (Pomegranate), Cynara scolymus (Artichoke), Coscinium fenestratum (Yellow vine) in Phytopharmacological, Molecular Biology Researches

Hypertension is a turning into a significant danger to the world. In the hunt of lead atoms from plant beginning as a substitute for poisonous engineered drugs, 26 Indian restorative plants and nourishments were screened for their ACE (Angiotensin Converting Enzyme) inhibitory movement. IC50 (half restraint of ACE) estimations of hydroalcoholic unrefined concentrates and division were dictated by a colorimetric technique. Dynamic parts were additionally screened to decide the compound energy, mode, explicitness and instrument of restraint. Normalization was finished by deciding aggregate phenolics and flavonoids as gallic corrosive and quercetin counterparts/mg of concentrate individually. Among 26 unrefined concentrates, Cynara scolymus extricate indicated the best action, IC50 esteem 356.62µg/mL. Pro restraint coming about because of protein precipitation was most noteworthy in Coscinium fenestratum. Lineweaver-Burk plots uncovered a serious method of restraint for Punica granatum ethyl acetic acid derivation part. Divisions of Cynara scolymus were seen as vague inhibitors of ACE. Coscinium fenestratum parts restrained the ACE by Zn2+ particle chelation. Further, in the quest for sheltered and powerful lead atoms from normal sources, (MP) Mucuna pruriens L. (Fabaceae) seeds were used for investigating the antihypertensive potential. Generally it is utilized as diuretic and Hypotensive. Bioassay-guided divisions were used for the separation of dynamic mixes by segment chromatography. IC50 esteem, protein energy and restraint system were resolved. In vivo time and portion subordinate hypotensive examination followed by changes in the MAP (Mean blood vessel pressure) actuated by angiotensin I (3 nmol/kg), angiotensin II (3nmol/kg), and to bradykinin (10nmol/kg) in anesthetized rodents was finished. Plasma and tissue ACE exercises were additionally decided. Phytochemical examination by spectroscopic methods uncovered the nearness of realized mixes like genistein, ursolic corrosive and L-DOPA from the ethyl acetic acid derivation and water part separately. In vitro examination uncovered MP ethyl acetic acid derivation portion (MPEA) and genistein as the most dynamic part (IC50 156.45µg/mL) and compound (IC50 253.81µM) individually. Lineweaver-Burk plots uncovered a non-serious method of hindrance. Expert protein precipitation was the recommended instrument for restraint. The concentrate indicated a time and portion subordinate decline in the MAP.

Low plasma angiotensin-converting enzyme 2 level in diabetics increases the risk of severe COVID-19 infection.

Patients with pre-existing chronic diseases are more susceptible to coronavirus disease 2019 (COVID-19), yet the underlying causes of increased risk are of infection remain unclear. Angiotensin-converting- enzyme 2 (ACE2), the cell surface receptor that recognizes the coronavirus spike protein has protective effects against inflammation and chronic hyperglycemia in animal models. The roles of ACE2 in severe SARS-CoV-2 infections remains ambiguous due to contradictory findings. In this study, we aimed to investigate the relationship between human plasma ACE2 levels in diabetics and the high risk of severe SARS-CoV-2 infection. First, the medical records of 245 patients with SARS-CoV-2-positive who have chronic diseases were analyzed. We also recruited 404 elderly subjects with comorbid chronic diseases such as diabetes mellitus, coronary heart disease, cerebrovascular disease, hypertension and obesity, and investigated the ACE2 plasma levels. Plasma concentrations of ACE2 were much lower (2973.83±2196.79 pg/mL) in diabetics with chronic disease than in healthy controls (4308.21±2352.42 pg/ml), and the use of hypoglycemia drugs was associated with lower circulating concentrations of ACE2 (P=1.49E-08). Diabetics with lower plasma levels of ACE2 may be susceptible to severe COVID-19. Our findings suggest that the poor prognosis in patients with diabetes infected with SARS-CoV-2 may be due to low circulating ACE2 levels.

A Low-Sodium Diet Boosts Ang (1-7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure.

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7) levels, promoting nitric oxide bioavailability and stimulating 3′-5′-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1–7) levels, nitric oxide bioavailability and cGMP production.