Introduction: Measurement of microRNA (miRNA) in aldosterone-producing adenoma (APA) tissue from primary aldosteronism (PA) patients show levels of the miR24-1 cluster miRNAs (i.e. miRNAs 24-1, 27b and 23b) are significantly reduced relative to normal adrenal tissue. Our previous studies also show that miRNA-24 directly targets CYP11B2 (aldosterone synthase) gene expression. Circulating miRNAs released into the bloodstream may be diagnostic biomarkers or signalling molecules. Here, we assessed whether circulating levels of miR24-1 cluster miRNAs differ significantly between PA patients and essential hypertensives, and whether they correlate with relevant phenotypic traits.
Methods: Patients with essential hypertension patients (n=18) were drawn from the British Genetics of Hypertension (BRIGHT) study and matched with 18 confirmed PA patients for age, gender and systolic blood pressure. Circulating miRNA was isolated from 200 μL EDTA plasma and analysed using quantitative realtime assays for miRNAs 24, 27b and 23b.
Results: PA patients had significantly increased circulating levels of miRNAs 24 (P<0.05) and 23b (P<0.0001) relative to primary hypertensive patients; there were also trends towards higher miRNA-27b but this was not significant. MiRNA-23b negatively correlated with diastolic pressure (P<0.05), left ventricular mass (P<0.01) and age (P<0.05). MiRNAs 27b and 23b positively correlated with BMI (P<0.05).
Conclusions: We have identified and validated increased circulating miR24-1 cluster miRNA levels in PA patients. These contrast with the significantly reduced levels of these miRNAs observed in APA tissue. Interestingly, miR-24 has been proposed to act as a feedback signal, repressing CYP11B2 expression when aldosterone levels are high. Therefore, increased secretion of these miRNAs into the circulation may be the result of high aldosterone levels and be intended to suppress its release. Future studies will examine the role of these miRNAs in the aetiology and pathology of PA.
20 - 23 May 2017
European Society of Endocrinology