ATHENA Study – The Role of Circulating Plasma MicroRNAs in Pediatric Patients with Untreated Primary Hypertension: Baseline Expression and Exercise-Induced Changes

BACKGROUND: The role of microRNA in primary hypertension remains unclear. This study examined the expression of microRNA-16, -21, -27a, -27b, -133a, and -145 in untreated hypertensive children, their response to aerobic exercise, and correlations with blood pressure and related parameters. METHODS: A pre-post study, observational, hypothesis generating study included 56 hypertensive (SG - study group) and 59 healthy children (CG - control group). Plasma microRNA levels and clinical, biochemical, blood pressure, vascular, and hypertension-mediated organ damage (HMOD) parameters were assessed before and after one session of standardized aerobic exercise. RESULTS: The baseline relative microRNA-27b (p < 0.001) and microRNA-133a (p = 0.018) expressions were significantly lower in the SG; similarly, after an exercise bout. After an exercise bout, the expression of microRNA-27b, -133a, and -145 increased in CG, whereas only the expression of microRNA-145 increased in SG. In SG, microRNA-16, -21, -27a, and -145 correlated positively with pre-exercise blood pressure. There were no correlations between the analyzed microRNA particles and parameters of HMOD. ROC analysis identified the best prognostic profile for relative microRNA-27b expression as a potential biomarker of the absence of primary hypertension. Multivariate analysis revealed the relative microRNA-16 expression as the only significant predictor of elevated diastolic blood pressure. CONCLUSIONS: MicroRNA-27b, as well as microRNA-133a, are underexpressed in children with PH. These particles may represent potential markers of hypertension in children and may also be associated with a lower burden of hypertension-related alterations. MicroRNA-16 may serve as a marker of diastolic hypertension.