Differential expression of vascular smooth muscle-modulating microRNAs in human peripheral blood mononuclear cells: novel targets in essential hypertension

Vascular smooth muscle cell (VSMC) phenotypic plasticity has a critical role in the pathophysiology of arterial remodeling in essential hypertension. MicroRNAs are emerging as potential biomarkers and therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-143, miR-145, miR-21, miR-133 and miR-1, which are implicated in VSMC phenotypic modulation, in 60 patients with essential hypertension and 29 healthy individuals. All patients underwent 24-h ambulatory blood pressure (BP) monitoring. MicroRNA levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed lower miR-143 (2.20 +/- 0.25 versus 4.19 +/- 0.57, P < 0.001), miR-145 (13.51 +/- 1.73 versus 22.38 +/- 3.31, P = 0.010) and miR-133 (8.15 +/- 1.32 versus 37.03 +/- 8.18, P < 0.001) and higher miR-21 (3.08 +/- 0.32 versus 2.06 +/- 0.31, P = 0.048) and miR-1 (33.94 +/- 5.19 versus 12.35 +/- 2.13 P = 0.006) expression levels compared with controls. In hypertensive patients, we observed correlations of miR-143 (r = -0.380, P = 0.003), miR-145 (r= -0.405, P = 0.001), miR-21 (r = -0.486, P < 0.001) and miR-133 (r = 0.479, P < 0.001) expression levels with 24-h diastolic BP. Furthermore, we observed correlations of miR-21 (r = -0.291, P = 0.024), miR-1 (r = -0.312, P = 0.015) and miR-133 (r = 0.310, P = 0.016) levels with the dipping status. Associations of miR-143 (r = -0.292, P = 0.025), miR-145 (r = -0.399, P = 0.002), miR-21 (r = -0.343, P = 0.008) and miR-133 (r = 0.370, P = 0.004) levels with 24-h mean pulse pressure were also found. Our data provide important evidence that VSMC-modulating microRNAs are closely related to essential hypertension in humans and they may represent potential therapeutic targets in essential hypertension.