MiR-21 and miR-133 levels in peripheral blood mononuclear cells associate with left ventricular diastolic dysfunction in patients with diastolic heart failure

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. However, there are limited data regarding their role in Left Ventricular (LV) diastolic dysfunction. The aim of this study is to investigate miR-21 and miR-133 levels in peripheral blood mononuclear cells in patients with LV diastolic dysfunction. Methods: We included 29 patients with symptoms and signs of heart failure who had LVEF >50% and evidence of LV diastolic dysfunction (19 males, aged 54±10 years. Blood samples were also obtained from 29 healthy volunteers for comparison (17 males, aged 52±8 years). All subjects underwent a complete echocardiographic study. 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 (3.2±0.45 versus 2.05±0.31, p < 0.05), while miR-133 levels were found to be lower (10.16±4.81 versus 37.03±8.18, p<0.05) in patients with LV diastolic dysfunction compared to healthy controls. MiR-21 levels showed strong negative correlations with E/e' (r=-0.41, p<0.001) while miR-133 levels showed strong positive correlations with E/e' (r=0.42, p<0.001). Conclusions: Patients with LV diastolic dysfunction were shown to have a strong relationship with miR-21 and miR-133 levels in peripheral blood mononuclear cells. Our findings contribute to the understanding of pathogenesis of diastolic heart failure and might offer a future therapeutic target