EXPRESSION OF MIRS 221, 222 AND 145 IN PERIPHERAL MONOCYTE CELLS OF ESSENTIAL HYPERTENSIVE PATIENTS

MicroRNAs (miRs) are highly conserved, short noncoding RNA
molecules that negatively regulate messenger RNA stability and/
or translational efficiency. Since miRs can control the expression
of many genes, their role appears central to the survival and functions
of many cells. Several miRs have been associated with cardiovascular
disease and protection.
miRs 221 and 222 (miR221/222) have been already identified in
several different cells types including endothelial cells, circulating
progenitor cells, and peripheral monocytes. In these cell types
miR221/222 participate in the differentiation and proliferation,
inhibiting cell migration and homing, also by inhibiting the synthesis
of the receptor for the Stem Cell Factor c-Kit. Moreover,
miR221/222 modulate different genes regulating the angiogenesis
and inflammation. We have already observed that miR221/222
were up-regulated in CVD patients increasing ROS production and
reducing angiogenesis.
miR145 was described in smooth muscle cells (SMCs), and more
recently also in peripheral monocyte cells, and its biological function
appears to be related to cell proliferation and phenotype. It
was shown that when miR145 is under-expressed, SMCs switch
from contractile to proliferative phenotype, accelerating the progression
of atherosclerosis.
Consistently, it can be proposed that miRs221/222 and miR145
act in an opposite manner: low miR145 expression with high
miRs221/222 expression promoting a trend toward cell migration,
proliferation, cell oxidative stress and atherogenesis; conversely, a
balanced miR145 and miRs221/222 expression result in lower cell
oxidative stress, cell migration and proliferation, and deceleration
of atherogenesis.
We evaluated the expression of miRs 145, 221 and 222 in peripheral
blood monocytes (Real Time-PCR) in 64 consecutively enrolled newly diagnosed, untreated hypertensive patients (aged between
21 and 52 years old) with no additional risk factors; 49 healthy
subjects were included as controls. Plasma lipids, fibrinogen and
C-reactive protein (CRP) levels, AS indices, including pulse way
velocity (PWV) and augmentation index (AIx) and carotid media
thickness (cIMT) were measured.
We found that on the average hypertensives presented with approximately
2-fold miR221/222 expression, whereas miR145 was
approximately 0.75-fold with respect to healthy controls. Furthermore,
miR expression correlates with several markers of vascular
involvement and risk factors. Total cholesterol (221: r=0.358,
p<0.005; 222: r=0.242, p<0.05; 145: r=-0.253, p<0.05), High density
lipoprotein-cholesterol (221: r=-0.618, p<0.001; 222: r=-0.693,
p<0.001; 145: r=0.645, p<0.001), Low density lipoprotein-cholesterol
(221: r=0.459, p<0.001; 222: r=0.349, p<0.005; 145: r=-0.353,
p<0.005), Fibrinogen (221: r=0.589, p<0.001; 222: r=0.774, p<0.001;
145: r=-0.661, p<0.01), CRP (221: r=0.429, p<0.001; 222: r=0.566,
p<0.001; 145: r=-0.462, p<0.001), Systolic blood pressure (221:
r=0.627, p<0.001; 222: r=0.543, p<0.001; 145: r=-0.571, p<0.001), Diastolic
blood pressure (221: r=0.534, p<0.001; 222: r=0.543, p<0.001;
145: r=-0.613, p<0.001), AIx 221: r=0.651, p<0.001; 222: r=0.701,
p<0.001; 145: r=-0.620, p<0.001, PWV (221: r=0.693, p<0.001; 222:
r=0.726, p<0.001; 145: r=-0.641, p<0.001), cIMT (221: r=0.397,
p<0.001; 222: r=0.443, p<0.001; 145: r=-0.456, p<0.001).
Multiple regression analysis indicated that miR145, miR221 and
miR222 expression are significantly influenced by Fibrinogen, SBP
and DBP; moreover, miR222 is also associated with CRP plasma
levels (p<0.001), and AS indices (AIx: p<0.001, PWV: p<0.005).
Although we found an inverse correlation between miR145 and
miRs221/222, miR145 showed a poor absolute predictive power
with respect to vascular indices.
In conclusion we can confirm the role