Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism

Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the iden...

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Autores principales:	Cristian A. Carvajal, Alejandra Tapia-Castillo, Jorge A. Pérez, Carlos E. Fardella
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	primary aldosteronism (PA) biomarker lipocalin miR-21-5p extracellular vesicles AGP1 Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/9cbcd30183054dba939ab3730414e4e5
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spelling	oai:doaj.org-article:9cbcd30183054dba939ab3730414e4e52021-11-05T15:08:18ZSerum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism1664-322410.3389/fimmu.2021.768734https://doaj.org/article/9cbcd30183054dba939ab3730414e4e52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.768734/fullhttps://doaj.org/toc/1664-3224Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo.AimTo evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA.Subjects and MethodsA cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9.ResultsPA and EH subjects have significantly higher SBP and DBP (p <0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p <0.05) than the CTL&EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p <0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 – 1.00], p <0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 – 1.00], p<0.001) to discriminate the PA condition from EH and controls.ConclusionSerum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.Cristian A. CarvajalCristian A. CarvajalCristian A. CarvajalAlejandra Tapia-CastilloAlejandra Tapia-CastilloAlejandra Tapia-CastilloJorge A. PérezJorge A. PérezJorge A. PérezCarlos E. FardellaCarlos E. FardellaCarlos E. FardellaFrontiers Media S.A.articleprimary aldosteronism (PA)biomarkerlipocalinmiR-21-5pextracellular vesiclesAGP1Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	primary aldosteronism (PA) biomarker lipocalin miR-21-5p extracellular vesicles AGP1 Immunologic diseases. Allergy RC581-607
spellingShingle	primary aldosteronism (PA) biomarker lipocalin miR-21-5p extracellular vesicles AGP1 Immunologic diseases. Allergy RC581-607 Cristian A. Carvajal Cristian A. Carvajal Cristian A. Carvajal Alejandra Tapia-Castillo Alejandra Tapia-Castillo Alejandra Tapia-Castillo Jorge A. Pérez Jorge A. Pérez Jorge A. Pérez Carlos E. Fardella Carlos E. Fardella Carlos E. Fardella Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
description	Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo.AimTo evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA.Subjects and MethodsA cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9.ResultsPA and EH subjects have significantly higher SBP and DBP (p <0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p <0.05) than the CTL&EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p <0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 – 1.00], p <0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 – 1.00], p<0.001) to discriminate the PA condition from EH and controls.ConclusionSerum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.
format	article
author	Cristian A. Carvajal Cristian A. Carvajal Cristian A. Carvajal Alejandra Tapia-Castillo Alejandra Tapia-Castillo Alejandra Tapia-Castillo Jorge A. Pérez Jorge A. Pérez Jorge A. Pérez Carlos E. Fardella Carlos E. Fardella Carlos E. Fardella
author_facet	Cristian A. Carvajal Cristian A. Carvajal Cristian A. Carvajal Alejandra Tapia-Castillo Alejandra Tapia-Castillo Alejandra Tapia-Castillo Jorge A. Pérez Jorge A. Pérez Jorge A. Pérez Carlos E. Fardella Carlos E. Fardella Carlos E. Fardella
author_sort	Cristian A. Carvajal
title	Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
title_short	Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
title_full	Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
title_fullStr	Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
title_full_unstemmed	Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
title_sort	serum alpha-1-acid glycoprotein-1 and urinary extracellular vesicle mir-21-5p as potential biomarkers of primary aldosteronism
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9cbcd30183054dba939ab3730414e4e5
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Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism

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