Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for Pre-Eclampsia: A Case-Control Study

Angiotensinogen exists in two distinct redox forms in plasma, the oxidized sulfhydryl-bridge form and the reduced, unbridged, free thiol form. The oxidized form of angiotensinogen compared to the free thiol form preferentially interacts with renin resulting in increased generation of angiotensin. Th...

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Veröffentlicht in:PloS one 2015-08, Vol.10 (8), p.e0135905-e0135905
Hauptverfasser: Rahgozar, Soheila, Amirian, Tayebeh, Qi, Miao, Shahshahan, Zahra, Entezar-E-Ghaem, Mansureh, Ghasemi Tehrani, Hatav, Miroliaei, Mehran, Krilis, Steven A, Giannakopoulos, Bill
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container_issue 8
container_start_page e0135905
container_title PloS one
container_volume 10
creator Rahgozar, Soheila
Amirian, Tayebeh
Qi, Miao
Shahshahan, Zahra
Entezar-E-Ghaem, Mansureh
Ghasemi Tehrani, Hatav
Miroliaei, Mehran
Krilis, Steven A
Giannakopoulos, Bill
description Angiotensinogen exists in two distinct redox forms in plasma, the oxidized sulfhydryl-bridge form and the reduced, unbridged, free thiol form. The oxidized form of angiotensinogen compared to the free thiol form preferentially interacts with renin resulting in increased generation of angiotensin. The predictive potential of the ratio of free-thiol to oxidized angiotensinogen in the plasma for pre-eclampsia was first suggested by the Read group in ref 10. We propose an improved method for determining the ratio and validate the method in a larger cohort of pregnant women. Plasma samples from 115 individuals with pre-eclampsia and from 55 healthy pregnant control subjects were collected sequentially over a 2 year period. Using two distinct enzyme-linked immunosorbent assays (ELISAs) the plasma levels of total and free thiol angiotensinogen were quantified. The oxidized angiotensinogen plasma level is derived by subtracting the level of free thiol, reduced angiotensinogen from the total angiotensinogen levels in the plasma. The relative proportion of free thiol angiotensinogen, expressed as a percentage of that observed with an in-house standard, is significantly decreased in pre-eclamptic patients (70.85% ± 29.49%) (mean ± SD) as compared to healthy pregnant controls (92.98 ± 24.93%) (mean ± SD) p ≤ 0.0001. The levels of total angiotensinogen did not differ between the two groups. Patients with pre-eclampsia had substantially lower levels of free thiol angiotensinogen compared to healthy pregnant controls, whilst maintaining similar total angiotensinogen levels in the plasma. Hence, elevated levels of plasma oxidized angiotensinogen may be a contributing factor to hypertension in the setting of pre-eclampsia.
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Amirian, Tayebeh ; Qi, Miao ; Shahshahan, Zahra ; Entezar-E-Ghaem, Mansureh ; Ghasemi Tehrani, Hatav ; Miroliaei, Mehran ; Krilis, Steven A ; Giannakopoulos, Bill</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1c87bfc6fd1171b522d6f1381bf2e8ebfd08945e3063735e0ba51b20c8c214ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Angiotensin</topic><topic>Angiotensinogen</topic><topic>Angiotensinogen - blood</topic><topic>Angiotensinogen - chemistry</topic><topic>Angiotensins</topic><topic>Biological Assay - methods</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Comparative analysis</topic><topic>Diagnosis</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Free radicals</topic><topic>Genetic aspects</topic><topic>Gynecology</topic><topic>Health risk assessment</topic><topic>Homocysteine</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Immunoassays</topic><topic>Immunology</topic><topic>Infectious diseases</topic><topic>Obstetrics</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Placenta</topic><topic>Plasma</topic><topic>Plasma levels</topic><topic>Pre-eclampsia</topic><topic>Pre-Eclampsia - blood</topic><topic>Pre-Eclampsia - diagnosis</topic><topic>Preeclampsia</topic><topic>Pregnancy</topic><topic>Renin</topic><topic>ROC Curve</topic><topic>Sample size</topic><topic>Sampling methods</topic><topic>Science</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rahgozar, Soheila</creatorcontrib><creatorcontrib>Amirian, Tayebeh</creatorcontrib><creatorcontrib>Qi, Miao</creatorcontrib><creatorcontrib>Shahshahan, Zahra</creatorcontrib><creatorcontrib>Entezar-E-Ghaem, Mansureh</creatorcontrib><creatorcontrib>Ghasemi Tehrani, Hatav</creatorcontrib><creatorcontrib>Miroliaei, Mehran</creatorcontrib><creatorcontrib>Krilis, Steven A</creatorcontrib><creatorcontrib>Giannakopoulos, Bill</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; 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The oxidized form of angiotensinogen compared to the free thiol form preferentially interacts with renin resulting in increased generation of angiotensin. The predictive potential of the ratio of free-thiol to oxidized angiotensinogen in the plasma for pre-eclampsia was first suggested by the Read group in ref 10. We propose an improved method for determining the ratio and validate the method in a larger cohort of pregnant women. Plasma samples from 115 individuals with pre-eclampsia and from 55 healthy pregnant control subjects were collected sequentially over a 2 year period. Using two distinct enzyme-linked immunosorbent assays (ELISAs) the plasma levels of total and free thiol angiotensinogen were quantified. The oxidized angiotensinogen plasma level is derived by subtracting the level of free thiol, reduced angiotensinogen from the total angiotensinogen levels in the plasma. 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subjects Adult
Angiotensin
Angiotensinogen
Angiotensinogen - blood
Angiotensinogen - chemistry
Angiotensins
Biological Assay - methods
Biology
Biomarkers
Biomarkers - blood
Care and treatment
Case-Control Studies
Comparative analysis
Diagnosis
Enzyme-Linked Immunosorbent Assay
Female
Free radicals
Genetic aspects
Gynecology
Health risk assessment
Homocysteine
Hospitals
Humans
Hypertension
Immunoassays
Immunology
Infectious diseases
Obstetrics
Oxidation-Reduction
Oxidative Stress
Patients
Physiological aspects
Placenta
Plasma
Plasma levels
Pre-eclampsia
Pre-Eclampsia - blood
Pre-Eclampsia - diagnosis
Preeclampsia
Pregnancy
Renin
ROC Curve
Sample size
Sampling methods
Science
Womens health
title Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for Pre-Eclampsia: A Case-Control Study
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