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

Abstract

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.

Hypertrophic and antihypertrophic microRNA levels in peripheral blood mononuclear cells and their relationship to left ventricular hypertrophy in patients with essential hypertension

“…We have previously reported that changes of microRNA levels in PBMCs of hypertensive patients are related to clinical parameters of the disease. (21,22) In the present study, we observed lower expression levels of miR-133a and miR-26b and M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 12 higher levels of miR-1, miR-208b, miR-499 and miR-21 in hypertensive patients compared with healthy controls. This indicates a dysregulation of these microRNAs in peripheral blood mononuclear cells that possibly reflect cardiovascular changes that happen in response to disease in hypertensive patients.…”

Circulating microRNAs and hypertension—from new insights into blood pressure regulation to biomarkers of cardiovascular risk

“…[18,19] Amongst hypertensive individuals, miR-21, miR-143, and miR-145 negatively correlated with 24-hour ambulatory mean blood pressure, mean DBP and mean pulse pressure; miR-133 positively correlated with each of these measures. [18] Whilst associations for 24-hour mean blood pressure and mean DBP were not provided for miR-9 or miR-126, both correlated positively with mean pulse pressure. [19] Finally, miR-9 (but not miR-126) also correlated positively with left ventricular mass index.…”

“…This analysis implicated miR-181a in pathways associated with mitochondrial respiratory function, immunity and inflammation. [16] In a similar approach, the Vardas laboratory focussed on microRNAs linked to vascular smooth muscle modulation, [18] hypertrophy and endothelial dysfunction [19] in animal and tissue models.…”

Effect of MicroRNA-30e on the Behavior of Vascular Smooth Muscle Cells via Targeting Ubiquitin-Conjugating Enzyme E2I

“…15 MiR-1 has also been shown to participate in VSMC differentiation and phenotypic regulation. 16 Many studies have indicated that the knockdown of microRNA-30e (miR-30e) substantially represses lung cancer cell growth and tumorigenicity in a dose-dependent manner, 17 and antagonizes the morphological changes and the migratory and invasive characteristics of carcinoma cells. 18 Other studies have shown miR-30e involvement in cancer cell proliferation, migration and invasion.…”