Abstract 18146: Circulating miRNAs In Patients With Coronary Artery Disease
MicroRNAs (miRNAs) are small RNAs that control gene expression. Besides their cell intrinsic function, recent studies demonstrated that miRNAs can be detected in circulating blood and that these circulating miRNAs might serve as disease biomarkers.
Methods and Results: In order to determine the regulation of miRNAs, we performed a miRNA profile using RNA isolated from n=8 healthy volunteers and n=8 patients with stable CAD that received state-of-the-art pharmacological treatment. Interestingly, most of the highly expressed miRNAs that were lower in the blood of patients with CAD are known to be expressed in endothelial cells (e.g. miR-126 and members of the miR-17∼92 cluster). To prospectively confirm these data, we measured selected miRNAs in plasma of 36 patients with CAD and 17 healthy volunteers (HC) by quantitative PCR. Consistent with the data obtained by the profile, circulating levels of miR-126 (HC versus CAD: 25% decrease; p=0.001), miR-17 (HC versus CAD: 13.9% decrease; p = 0.004), miR-92a (HC: versus CAD: 20% decrease; p = 0.028) and the inflammation associated miR-155 (HC versus CAD: 71.2% decrease; p = 0.001) were significantly reduced in patients with CAD compared to healthy controls. Likewise, the smooth muscle enriched miR-145 (HC versus CAD: 29.8% decrease p= 0.001) was significantly reduced. In contrast, cardiac muscle-enriched miRNAs miR-133a (CAD versus HC: 45.5% increase; p=0.017) and miR-208a (CAD versus HC: 248% increase; p = 0.01) tend to be higher in patients with CAD. Prospective validation of the findings was performed in a validation cohort of additional 45 patients, which gave essentially identical results.
Conclusions: Circulating levels of vascular and inflammation-associated miRNAs are differentially regulated compared to cardiac muscle-derived miRNAs in patients with CAD. Further studies are necessary to determine the role of circulating miRNAs as biomarkers of cardiovascular diseases.
- © 2010 by American Heart Association, Inc.