Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, piso 4, Santiago, 8330077, Chile.
Centro Traslacional de Endocrinología (CETREN-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.
J Transl Med. 2019 Nov 27;17(1):392. 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.
“非经典”表观盐皮质激素过多症（NC-AME）在大约 7%的普通人群中被发现。这种表型的特征是低血浆肾素活性（PRA）、血清皮质醇（F）与皮质酮（E）比值高、皮质酮低、钾排泄分数（FEK）高和正常升高的收缩压（SBP）。早期发现和/或鉴定这种表型的新型生物标志物可以避免进展或导致动脉高血压的未来并发症。在特定的生物流体中分离细胞外囊泡，如外泌体，支持组织特异性 RNA 和 miRNA 的鉴定，这些 RNA 和 miRNA 可能作为新型生物标志物有用。我们的目的是鉴定与 NC-AME 表型相关的尿外泌体中的 miRNA。
我们在智利的一个初级保健队列中进行了一项横断面研究。我们测量了血压、血清皮质醇、皮质酮、醛固酮、PRA。根据之前的报道，将一部分受试者分为 NC-AME 组（n=10）。通过 Illumina-NextSeq-500 对尿外泌体中的 miRNA 进行测序。
我们发现 NC-AME 组的皮质酮（p<0.0001）、F/E 比值（p<0.0001）、血清钾（p=0.009）和 24 小时 FEK（p=0.03）均较低。我们发现 miR-204-5p（fold-change=0.115；p<0.001）和 miR-192-5p（fold-change=0.246；p<0.03）在 NC-AME 中均显著下调。miR-192-5p 的表达与 PRA 呈正相关（r=0.45；p<0.028），miR-204-5p 的表达与 SBP（r=-0.48；p<0.027）和 F/E 比值（r=-0.48；p<0.026）呈正相关。
这些发现可能支持这些 miRNA 作为 NC-AME 表型的调节剂和新型生物标志物的潜在作用。
