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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Nov 22

PMID 34804057

Citations 3

Authors

Cristian A Carvajal

Alejandra Tapia-Castillo

Jorge A Perez

Carlos E Fardella

Affiliations

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Abstract

Aim: To evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA.

Subjects And Methods: A 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.

Results: PA 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.

Conclusion: Serum 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.

Citing Articles

Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism.

Bertolone L, Castagna A, Manfredi M, De Santis D, Ambrosani F, Antinori E Front Endocrinol (Lausanne). 2023; 14:1096441.

PMID: 37223008 PMC: 10200877. DOI: 10.3389/fendo.2023.1096441.

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia.

Concistre A, Petramala L, Circosta F, Romagnoli P, Soldini M, Bucci M Front Cardiovasc Med. 2022; 9:930959.

PMID: 35966515 PMC: 9366211. DOI: 10.3389/fcvm.2022.930959.

Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess.

Tapia-Castillo A, Carvajal C, Perez J, Fardella C Endocrine. 2022; 77(2):380-391.

PMID: 35676467 DOI: 10.1007/s12020-022-03103-x.

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