Circulating Toll-like receptor 4-responsive microRNA panel in patients with coronary artery disease: results from prospective and randomized study of treatment with renin-angiotensin system blockade.

Abstract

The extracellular miRNAs circulate in the bloodstream and may serve as novel diagnostic and therapeutic biomarkers. The aim of the present study was to investigate circulating Toll-like receptor 4 (TLR4)-responsive miRNA expression in patients with coronary artery disease (CAD) and to examine the effects of renin-angiotensin system (RAS) blockade and statins on miRNA levels. This study included 41 patients with CAD and 20 subjects without CAD (non-CAD). Plasma TLR4-responsive miRNA samples were analysed using a microarray assay for 1700 human miRNA. The candidate miRNAs were verified with real-time reverse transcription (RT)-PCR. Patients with CAD were randomized to 12 months of combined treatment with either telmisartan and atorvastatin [angiotensin II receptor blocker (ARB)] or enalapril and atorvastatin [angiotensin-converting enzyme inhibitor (ACEI)]. Plasma samples were obtained from peripheral blood at baseline and after 12 months. The microarray assay showed significant differences in seven TLR4-responsive miRNAs between the CAD and non-CAD groups (P<0.05). Real-time PCR verified that miR-31, miR-181a, miR-16 and miR-145 were significantly lower in the CAD group than in the non-CAD group (P<0.01). Levels of TLR4 protein were higher in the CAD group than in the non-CAD group (P<0.01) and were negatively correlated with levels of TLR4-responsive miRNAs. Receiver operating characteristic (ROC) curve analysis revealed that a panel of these four miRNAs was sensitive and specific enough to distinguish CAD from non-CAD [area under the curve (AUC)=0.93, 95% CI (confidence interval)=0.99-0.87]. Both ARB and ACEI groups showed increased TLR4-responsive miRNAs and diminished levels of TLR4 protein (P<0.05). Changes in miRNAs and TLR4 levels were greater in the ARB group than in the ACEI group (P<0.05). Circulating TLR4-responsive miRNAs including miR-31, miR-181a, miR-16 and miR-145 were significantly lower in patients with CAD compared with controls and these miRNAs may be involved in the pathogenesis of CAD.

• Authors: Mamoru Satoh, Yuji Takahashi, Tsuyoshi Tabuchi, Makiko Tamada, Kan Takahashi, Tomonori Itoh, Yoshihiro Morino, Motoyuki Nakamura
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 128 Issue 8 Pg. 483-91 (Apr 2015) ISSN: 1470-8736 [Electronic] England
• PMID: 25385173 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• MicroRNAs
• TLR4 protein, human
• Toll-Like Receptor 4

Topics

• Aged
• Angiotensin Receptor Antagonists (pharmacology, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Coronary Artery Disease (blood, drug therapy, genetics)
• Female
• Gene Expression Profiling
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Prospective Studies
• Renin-Angiotensin System (drug effects)
• Toll-Like Receptor 4 (blood)