Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

AbstractIntroduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.

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Decreased Plasma Levels of Angiotensin-Converting Enzyme Among Patients With Bipolar Disorder

Frontiers in Neuroscience ◽

10.3389/fnins.2021.617888 ◽

2021 ◽

Vol 15 ◽

Author(s):

Marsal Sanches ◽

Gabriela D. Colpo ◽

Valeria A. Cuellar ◽

Taya Bockmann ◽

Deevakar Rogith ◽

...

Keyword(s):

Bipolar Disorder ◽

Angiotensin Converting Enzyme ◽

Plasma Levels ◽

Renin Angiotensin System ◽

Cross Sectional Study ◽

Healthy Controls ◽

Converting Enzyme ◽

Cross Sectional ◽

Angiotensin Converting Enzyme 2 ◽

Therapeutic Implications

BackgroundDysfunctions in the renin-angiotensin system (RAS) seem to be involved in the pathophysiology of several mental illness, including schizophrenia and mood disorders. We carried out a cross-sectional study assessing the levels of RAS-related molecules among bipolar disorder (BD) patients compared to healthy controls.Methodsour sample consisted of 30 outpatients with BD type 1 (10 males, 20 females, age = 35.53 ± 10.59 years, 14 euthymic, 16 experiencing mood episodes) and 30 healthy controls (10 males, 20 females, age = 34.83 ± 11.49 years). Plasma levels of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin-II (Ang II), and angiotensin (1–7) [Ang-(1–7)] were determined by ELISA.ResultsBD patients experiencing ongoing mood episodes had significantly lower ACE levels compared to controls (median: 459.00 vs. 514.10, p < 0.05). There was no association between the levels of these biomarkers and clinical parameters.ConclusionOur findings support the involvement of RAS dysfunction in the pathophysiology of BD. Considering the potential therapeutic implications linked to a better understanding of the role of RAS dysfunction in BD, studies allowing a better characterization of RAS-related molecules level and activity across different mood states are of high interest.

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Increased ischemia-modified albumin levels in children with steroid-sensitive nephrotic syndrome

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.7.2924 ◽

2020 ◽

Vol 36 (7) ◽

Author(s):

Gokhan Cakirca ◽

Ahmet Guzelcicek ◽

Kenan Yilmaz ◽

Cemal Nas

Keyword(s):

Oxidative Stress ◽

Nephrotic Syndrome ◽

Pediatric Nephrology ◽

Cross Sectional Study ◽

Healthy Controls ◽

Cross Sectional ◽

Ischemia Modified Albumin ◽

Creative Commons ◽

Steroid Sensitive Nephrotic Syndrome ◽

Steroid Sensitive

Objective: Growing evidence shows that oxidative stress plays an important role in the development and progression of nephrotic syndrome (NS). In this study, we aimed to examine serum IMA levels as an indicator of oxidative stress in children with steroid-sensitive NS (SSNS) in remission and relapse. Methods: This cross-sectional study was carried out at the Pediatric Nephrology Unit of Sanliurfa Training and Research Hospital, Sanliurfa, Turkey, from April 2019 to December 2019. In this study Serum IMA and albumin levels were determined in 70 children with SSNS and 45 healthy controls. Among the children with SSNS, 50 were in remission and 20 were in relapse. Then, adjusted IMA levels were calculated from the IMA/albumin ratio. Results: IMA and adjusted IMA levels significantly increased and albumin significantly decreased in children with SSNS in relapse and remission compared with those of the healthy controls. Moreover, these alterations were more prominent in the relapse group than in the remission group. IMA was inversely correlated with albumin in children with SSNS (r= −0.881, p= <0.001). Conclusions: Our findings demonstrated that elevated IMA and adjusted IMA levels observed in patients with SSNS were associated with increased oxidative stress and could indirectly reflect the degree of oxidative damage in glomerular structures. doi: https://doi.org/10.12669/pjms.36.7.2924 How to cite this:Cakirca G, Guzelcicek A, Yilmaz K, Nas C. Increased ischemia-modified albumin levels in children with steroid-sensitive nephrotic syndrome. Pak J Med Sci. 2020;36(7):---------. doi: https://doi.org/10.12669/pjms.36.7.2924 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Interactions of Renin-Angiotensin System and COVID-19: The Importance of Daily Rhythms in ACE2, ADAM17 and TMPRSS2 Expression

Physiological Research ◽

10.33549/physiolres.934754 ◽

2021 ◽

pp. S177-S194

Author(s):

J ZLACKÁ ◽

K STEBELOVÁ ◽

M ZEMAN ◽

I HERICHOVÁ

Keyword(s):

Renin Angiotensin System ◽

Positive Association ◽

Ang Ii ◽

Virus Envelope ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Renin Angiotensin ◽

Circadian Control ◽

A Disintegrin And Metalloproteinase

Angiotensin-converting enzyme 2 (ACE2) was identified as a molecule that mediates the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several membrane molecules of the host cell must cooperate in this process. While ACE2 serves in a membrane receptor-mediating interaction with the surface spike (S) glycoprotein of SARS-CoV-2 located on the virus envelope, enzyme A disintegrin and metalloproteinase 17 (ADAM17) regulates ACE2 availability on the membrane and transmembrane protease serine 2 (TMPRSS2) facilitates virus-cell membrane fusion. Interestingly, ACE2, ADAM17 and TMPRSS2 show a daily rhythm of expression in at least some mammalian tissue. The circadian system can also modulate COVID-19 progression via circadian control of the immune system (direct, as well as melatonin-mediated) and blood coagulation. Virus/ACE2 interaction causes ACE2 internalization into the cell, which is associated with suppressed activity of ACE2. As a major role of ACE2 is to form vasodilatory angiotensin 1-7 from angiotensin II (Ang II), suppressed ACE2 levels in the lung can contribute to secondary COVID-19 complications caused by up-regulated, pro-inflammatory vasoconstrictor Ang II. This is supported by the positive association of hypertension and negative COVID-19 prognosis although this relationship is dependent on numerous comorbidities. Hypertension treatment with inhibitors of renin-angiotensin system does not negatively influence prognosis of COVID-19 patients. It seems that tissue susceptibility to SARS-CoV-2 shows negative correlation to ACE2 expression. However, in lungs of infected patient, a high ACE2 expression is associated with better outcome, compared to low ACE2 expression. Manipulation of soluble ACE2 levels is a promising COVID-19 therapeutic strategy.

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Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

Acta Endocrinologica ◽

10.1530/eje-19-0379 ◽

2019 ◽

Vol 181 (5) ◽

pp. 481-488 ◽

Cited By ~ 3

Author(s):

Lee S Nguyen ◽

Nathalie Rouas-Freiss ◽

Christian Funck-Brentano ◽

Monique Leban ◽

Edgardo D Carosella ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Critical Role ◽

Renin Angiotensin System ◽

Cross Sectional Study ◽

Healthy Controls ◽

Sectional Study ◽

Adrenal Hyperplasia ◽

Cross Sectional ◽

Adequate Model ◽

Soluble Hla

Background HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency. Methods In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data. Results Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35–1.27) and −0.44 (−0.94, −0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04–0.41), P = 0.001) and estradiol (β = −0.22 (−0.57, −0.02), P < 0.001). Conclusion CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.

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Oral health conditions in children with idiopathic nephrotic syndrome: a cross-sectional study

BMC Oral Health ◽

10.1186/s12903-020-01197-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Urszula Kaczmarek ◽

Alina Wrzyszcz-Kowalczyk ◽

Katarzyna Jankowska ◽

Katarzyna Prościak ◽

Monika Mysiak-Dębska ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Oral Health ◽

Idiopathic Nephrotic Syndrome ◽

Cross Sectional Study ◽

Health Conditions ◽

Sectional Study ◽

Cross Sectional

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No evidence for altered plasma NGF and BDNF levels in fibromyalgia patients

Scientific Reports ◽

10.1038/s41598-019-49403-7 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

David Baumeister ◽

Wolfgang Eich ◽

Silvia Saft ◽

Olga Geisel ◽

Rainer Hellweg ◽

...

Keyword(s):

Growth Factor ◽

Bayesian Methods ◽

Cross Sectional Study ◽

Peripheral Sensitization ◽

Healthy Controls ◽

Plasma Samples ◽

Sectional Study ◽

Cross Sectional ◽

Bayesian Approaches

Abstract There has been a surging interest in the putative role of peripheral growth factors in the pathophysiology of fibromyalgia, specifically in the peripheral sensitization that occurs in chronic pain disorders. This cross-sectional study set out to assess and compare brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in plasma samples from fibromyalgia patients and healthy controls. Plasma BDNF and NGF were measured in 89 fibromyalgia patients and 36 pain-free controls, and compared using ANCOVA controlling for potential confounders, as well as Bayesian methods for parameter estimation and model evaluation. BDNF and NGF levels in fibromyalgia patients did not differ from those in pain-free controls. Statistical methods were consistent, with both frequentist and Bayesian approaches leading to the same conclusions. Our study fails to replicate the finding that peripheral BDNF is altered in fibromyalgia, and instead our findings suggest that plasma levels of growth factor appear normative in fibromyalgia.

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Ocular and extra-ocular complications following long-term steroid consumption in children with idiopathic nephrotic syndrome

BIRDEM Medical Journal ◽

10.3329/birdem.v11i1.51023 ◽

2020 ◽

Vol 11 (1) ◽

pp. 7-10

Author(s):

Gulshan Nigar Chaudhury ◽

Tarannum Khandaker ◽

Tahmina Ferdous ◽

Rifat Asma Chowdhury ◽

Shireen Afroz ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Intraocular Pressure ◽

Bone Pain ◽

Idiopathic Nephrotic Syndrome ◽

Epigastric Pain ◽

Cross Sectional Study ◽

High Dose ◽

Ocular Complications ◽

Cross Sectional ◽

The Mean

Background: High dose of corticosteroids are required by patients with idiopathic nephrotic syndrome for long duration due to repeated relapse. The aims of this study were to analyze the ocular and extra-ocular complications of steroids on children with nephrotic syndrome. Methods: This cross-sectional study was conducted at Dhaka Shishu (Children) Hospital from September 2017 to September 2019. Children with nephrotic syndrome between 1-16 years of age, who received steroid for at least three months, participated in this study. Total 70 children were enrolled. Detailed history was taken from parents regarding initial episode, drug history, visual problem, headache, hypertension, weight gain, psychosis, bone pain, epigastric pain and excessive growth of body hair. Comprehensive opthalmologic assessment including visual acquity, intraocular pressure and cataract were performed. Detail of renal histopathology and treatment regimen in each patient was noted. Results: A total of 70 patients were included, 61.4% were male and 38.6% were female. Median age at the time of examination was 60 months (range 17 to 216 months). The mean duration of disease was 33.71±21.12 months. The mean cumulative steroid dose at the time of examination was 8485.91±7326.83 mg. Fourteen (20%) patients had posterior subcapsular cataract. Among 70 patients, we could do visual acuity for 25 (35.7%) patients, intraocular pressure (IOP) in mm for 51 (72.85%) patients. Among them raised IOP was found in five (9.8%) patients. In right eye mean IOP was 14.16±3.57 and for left eye 14.77±3.55 mm. Renal biopsy was performed in 15 (21.43%) cases. Among the biopsy report, it was found that mesangial proliferative glomerulonephritis (MPGN) in 8 (53.33%), focal segmental glomerulonephritis (FSGS) in 2 (13.33%) and minimal change in 5 (33.34%) cases. Among all cases, 12 (17.14%) patients developed Cushingoid facies, 3 (4.2%) patients had hypertrichosis, 3 (4.2%) patients had central obesity and 4 (5.7%) patients had buffalo hump but none had hypertension, diabetes mellitus, epigastric pain, bone pain or psychosis. Conclusion: Cataract formation was the most frequent ocular complication after large dose of oral corticosteroid therapy. The present study emphasizes the need for regular eye screening. Cushingoid facies was the most frequent among extra-ocular complications. Birdem Med J 2021; 11(1): 7-10

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ACE2 in the renin–angiotensin system

Clinical Science ◽

10.1042/cs20200478 ◽

2020 ◽

Vol 134 (23) ◽

pp. 3063-3078 ◽

Cited By ~ 1

Author(s):

Thiago Verano-Braga ◽

Ana Luiza Valle Martins ◽

Daisy Motta-Santos ◽

Maria José Campagnole-Santos ◽

Robson Augusto Souza Santos

Keyword(s):

Recent Literature ◽

Renin Angiotensin System ◽

Ang Ii ◽

Critical Component ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Critical View ◽

Renin Angiotensin ◽

20Th Anniversary

Abstract In 2020 we are celebrating the 20th anniversary of the angiotensin-converting enzyme 2 (ACE2) discovery. This event was a landmark that shaped the way that we see the renin–angiotensin system (RAS) today. ACE2 is an important molecular hub that connects the RAS classical arm, formed mainly by the octapeptide angiotensin II (Ang II) and its receptor AT1, with the RAS alternative or protective arm, formed mainly by the heptapeptides Ang-(1-7) and alamandine, and their receptors, Mas and MrgD, respectively. In this work we reviewed classical and modern literature to describe how ACE2 is a critical component of the protective arm, particularly in the context of the cardiac function, coagulation homeostasis and immune system. We also review recent literature to present a critical view of the role of ACE2 and RAS in the SARS-CoV-2 pandemic.

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Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Journal of Endocrinology ◽

10.1530/joe-12-0341 ◽

2012 ◽

Vol 216 (2) ◽

pp. R1-R17 ◽

Cited By ~ 266

Author(s):

Robson A S Santos ◽

Anderson J Ferreira ◽

Thiago Verano-Braga ◽

Michael Bader

Keyword(s):

Renin Angiotensin System ◽

Biologically Active ◽

Ang Ii ◽

Converting Enzyme ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Renin Angiotensin ◽

Potential Interactions ◽

G Protein Coupled

Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin–angiotensin system (RAS). Ang-(1–7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1–7) synthesis. This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1–7). Thus, the axis formed by ACE2/Ang-(1–7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/proliferative arm of the RAS consisting of ACE, Ang II, and AT1receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1–7) and Mas with AT1and AT2receptors.

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