Renin-sensitive microRNAs correlate with atherosclerosis plaque progression.
Author(s): Deiuliis J(1), Mihai G(1), Zhang J(2), Taslim C(2), Varghese JJ(1), Maiseyeu
A(1), Huang K(2), Rajagopalan S(1).
Affiliation(s): Author information:
(1)Davis Heart & Lung Research Institute, The Ohio State University College of
Medicine, Columbus, OH, USA. (2)Department of Biomedical Informatics, The Ohio
State University College of Medicine, Columbus, OH, USA.
Publication date & source: 2014, J Hum Hypertens. , 28(4):251-8
Recent trials with inhibition of the renin-angiotensin-aldosterone system (RAAS)
in patients with established atherosclerosis have been equivocal. MicroRNAs
(miRs) are known to affect multiple pathways relevant to atherosclerosis,
including RAAS. We postulated that the use of a direct renin antagonist would
result in differential regulation of miRs. We examined monocyte miR expression
before and after treatment with renin antagonist, Aliskiren, in patients with
established cardiovascular disease as part of a prospective, single-center,
randomized, double-blind and placebo-controlled clinical trial (NCT01417104).
After screening, patients (mean age 62±3 years) were randomized to placebo or
Aliskiren. Three-dimensional dark-blood magnetic resonance imaging assessment of
atherosclerosis in the thoracic and abdominal aorta was conducted at baseline and
at study completion (19-36 weeks). MiR expression arrays were performed on RNA
from peripheral blood mononuclear cells collected at baseline and 12 weeks
following randomization to placebo or Aliskiren and showed that hsa-miR-106b-5p,
27a-3p and 18b-5p were significantly downregulated with Aliskiren. Baseline
expression of these miRs positively correlated with normalized total wall volume
in subjects taking Aliskiren (miR-106b, R=0.62; miR-27a, R=0.63; miR-18b, R=0.77;
P<0.05). Hsa-miR-106b-5p, 27a-3p and 18b-5p may represent pathway-specific
adaptations to renin inhibition relevant to atherosclerosis.
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