Author + information
- Jeffrey Deiuliis,
- Georgeta Mihai,
- Jie Zhang,
- Juliet Varghese,
- Andrei Maiseyeu,
- Orlando Simonetti,
- Kun Huang and
- Sanjay Rajagopalan
Renin-angiotensin-aldosterone (RAS) blockade has been demonstrated to have favorable effects in atherosclerosis. microRNA's (miR) may affect multiple pathways relevant to atherosclerosis including those regulated by RAS pathways. We postulated that complete RAS blockade may result in differential regulation of miR's that may be informative of renin-sensitive pathways and examined monocyte miR expression before and following treatment with aliskiren as part of a prospective trial.
This was a single-center, randomized, double-blind, placebo-controlled clinical trial (NCT01417104) in patients with established cardiovascular disease. Patients were randomized to placebo (n=37, age 64.5±8.9 years) or aliskiren 300 mg qd (n=34, age 63.9±11.5 years). At baseline and 12 weeks of treatment blood monocytes were collected for miR expression, while 3D-dark blood MRI assessment of atherosclerosis in the aorta was conducted at baseline and at study completion (19-36 weeks). miRNA expression arrays (Nanostring Technologies) were performed on monocyte mRNA. miR expression was normalized (global sum) and significantly changed (>1.5-fold, p<0.05) miRs were assessed for correlation with changes in atheroma volume in the trial.
Three down-regulated miRs (hsa-miR-106b-5p, −27a-3p, and −18b-5p) were identified in patients after aliskiren administration. These miRs did not change in control patients receiving placebo. Baseline miR expression correlated significantly with increased normalized total wall volume (thoracic and abdominal) in subjects taking aliskiren (miR-106b, R=0.62; miR-27a, R=0.63; miR-18b, R=0.77, p<0.05 for all 3). Correlation was maintained when examined in those patients on ACEI/ARB therapy at baseline.
Selective down-regulation of hsa-miR-106b-5p, −27a-3p, and −18b-5p in patients on renin blockade may represent pathway-specific adaptations to complete inhibition of the RAS system. The significance of these findings needs to be determined.
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Preclinical Manifestations of Hypertension and Arterial Stiffness
Abstract Category: 25. Prevention: Hypertension
Presentation Number: 1276-22
- 2013 American College of Cardiology Foundation