Renin-sensitive microRNAs correlate with atherosclerosis plaque progression

Area of Science:

• Cardiovascular Medicine
• Molecular Biology
• Pharmacology

Background:

• Renin-angiotensin-aldosterone system (RAAS) inhibition trials for atherosclerosis have yielded mixed results.
• MicroRNAs (miRs) are implicated in atherosclerosis pathways, including RAAS.
• The effect of direct renin antagonism on miR regulation in atherosclerosis is not well understood.

Purpose of the Study:

• To investigate the impact of the direct renin antagonist Aliskiren on microRNA expression in patients with established cardiovascular disease.
• To determine if changes in specific miRs correlate with atherosclerosis progression during renin inhibition.

Main Methods:

• A prospective, randomized, double-blind, placebo-controlled trial (NCT01417104) involving patients with established cardiovascular disease.
• Assessment of thoracic and abdominal aorta atherosclerosis using 3D dark-blood MRI at baseline and study completion.
• Analysis of peripheral blood mononuclear cell (PBMC) microRNA expression arrays before and after 12 weeks of Aliskiren or placebo treatment.

Main Results:

• Aliskiren treatment led to significant downregulation of hsa-miR-106b-5p, hsa-miR-27a-3p, and hsa-miR-18b-5p.
• Baseline expression levels of these downregulated miRs positively correlated with normalized total aortic wall volume in the Aliskiren group.
• Correlations were observed for miR-106b (R=0.62), miR-27a (R=0.63), and miR-18b (R=0.77), all with P<0.05.

Conclusions:

• Aliskiren treatment induces differential microRNA expression changes in patients with cardiovascular disease.
• Hsa-miR-106b-5p, hsa-miR-27a-3p, and hsa-miR-18b-5p may serve as biomarkers for pathway-specific adaptations to renin inhibition in atherosclerosis.
• These findings contribute to understanding the molecular mechanisms linking RAAS inhibition and atherosclerosis.