MiR-1, miR-9 and miR-126 levels in peripheral blood mononuclear cells of patients with essential hypertension associate with prognostic indices of ambulatory blood pressure monitoring

Abstract

Purpose: MicroRNAs (miRs) are essential regulators of gene expression implicated in cardiovascular function and disease. MiR-21 and miR-133 have been shown to play a role in heart hypertrophy and fibrosis. They have also been shown to regulate proliferation and phenotypic switch of Vascular Smooth Muscle Cells, which have a critical role in the development of hypertension. Ambulatory blood pressure monitoring (ABPM) is a useful tool for evaluating 24-hour blood pressure profile and a good predictor of target organ damage in hypertensive patients. We evaluated miR-21 and miR-133 levels in peripheral blood mononuclear cells of patients with essential hypertension in relation to ABPM parameters. Methods: 24-hour ABPM and blood sampling were obtained in 60 untreated hypertensive patients (29 males, aged 60.42±9.6 years). Blood samples were also obtained from 29 healthy volunteers (13 males, aged 56.69±8.59 years) for comparison. Peripheral blood mononuclear cells (PBMCs) were isolated and microRNA levels were determined by quantitative real time reverse transcription PCR. Results: MiR-21 levels were found to be higher (3.08±0.32 versus 2.05±0.31, p0.048), while miR-133 levels were found to be lower (8.15±1.32 versus 37.03±8.18, p<0.001) in hypertensive patients compared to healthy controls. In hypertensive patients, miR-21 levels showed strong negative correlations with 24-hour diastolic blood pressure (r=-0.486, p<0.001) as well with 24-hour mean blood pressure (r=-0.419, p=0.001). Significant negative correlations were also observed between miR-21 levels and 24-hour mean pulse pressure (r=-0.343, p=0.008) as well as mean 24-hour dipping status (r=-0.291, p=0.024). MiR-133 levels showed strong positive correlations with 24-hour diastolic blood pressure (r=0.479, p<0.001) as well with 24-hour mean blood pressure (r=0.395, p=0.002) in hypertensive patients. Significant positive correlations were also observed between miR-133 levels and 24-hour mean pulse pressure (r=0.370, p=0.004) as well as mean 24-hour dipping status (r=0.310, p=0.016). Conclusions: MiR-21 and miR-133 levels in PBMCs of hypertensive patients differ from healthy controls and show strong correlations with blood pressure parameters derived from 24-hour ABPM. Correlations with 24h pulse pressure and with dipping status might indicate a possible implication of these microRNAs in target organ damage. Our data define miR-21 and miR-133 as possible candidate biomarkers as well as possible therapeutic targets in hypertension.