Downregulation of exosomal miR-192-5p and miR-204-5p in subjects with nonclassic apparent mineralocorticoid excess

• Published in: Journal of translational medicine Vol. 17; no. 1; p. 392
• Main Authors: Tapia-Castillo, Alejandra, Guanzon, Dominic, Palma, Carlos, Lai, Andrew, Barros, Eric, Allende, Fidel, Vecchiola, Andrea, Fardella, Carlos E, Salomón, Carlos, Carvajal, Cristian A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.11.2019; BioMed Central; BMC
• Subjects: Adolescent; Adult; Aldosterone; Angiotensin II; Biological markers; Biomarkers; Blood pressure; Case-Control Studies; Child; Complications; Cortisol; Cortisone; Down-Regulation - genetics; Endocrine disorders; Enzymes; Exosomes; Exosomes - genetics; Exosomes - ultrastructure; Female; Gene expression; Genotype & phenotype; Glucocorticoids; Hormones; Humans; Hypertension; Male; Metabolism; Metabolites; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy; Middle Aged; Mineralocorticoid Excess Syndrome, Apparent; Mineralocorticoid Excess Syndrome, Apparent - genetics; Mineralocorticoid Excess Syndrome, Apparent - urine; Mineralocorticoid receptor; miRNA; Nanoparticles; Nonclassic AME; Novels; Particle size; Phenotypes; Potassium; Primary care; Proteins; Renin; Reproducibility of Results; RNA; Urine; Young Adult; United States > US; Hypertension; Nonclassic AME; MicroRNA; Exosomes; Mineralocorticoid receptor
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-019-02143-8

The "nonclassic" apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n = 10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500. We found that NC-AME subjects had lower cortisone (p < 0.0001), higher F/E ratio (p < 0.0001), lower serum potassium (p = 0.009) and higher FEK 24 h (p = 0.03) than controls. We found miR-204-5p (fold-change = 0.115; p 0.001) and miR-192-5p (fold-change = 0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r = 0.45; p 0.028) and miR-204-5p expression with SBP (r = - 0.48, p 0.027) and F/E ratio (r = - 0.48; p 0.026). These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.