Abstract 17341: Deep Sequencing Analysis of Myocardial and Circulating microRNA Profiles in Patients with Advanced Heart Failure and Controls
Background: MicroRNA (miRNA) profiles in patients with heart failure (HF) show considerable differences compared to normal cardiac profiles. Recently, several cardiac-specific miRNAs have been described in peripheral blood samples from patients with HF. The aim of our study was the direct comparison of miRNA profiles in cardiac tissue specimens and corresponding plasma samples of patients with HF and controls.
Methods: Total RNA was extracted from cardiac tissue samples collected during cardiac surgery from 38 patients with HF including 17 paired samples taken at implantation and explantation of a left ventricular assist device (LVAD), and 8 non-diseased control hearts. Plasma was available from 7 HF patients before and after LVAD placement and from 4 controls. Small RNA libraries were multiplexed and sequenced on the Illumina HiSeq 2000 sequencer, and analyzed using an in-house annotation pipeline. Differential expression was defined by an adjusted p-value of smaller than 0.05 (FDR).
Results: 380 million reads were obtained from the myocardial samples of which 76 % represented miRNAs and 49 million reads from the plasma samples of which 69 % were miRNAs. Profiles of miRNAs in HF patients showed concordant and discordant changes in the tissue and plasma samples. Corresponding concordant changes in myocardial tissue and plasma samples were limited to upregulation of, miR-195 (log2 fold change (FC) in plasma 4.394 , q-value 0.0001122; FC in tissue 0.7171, q-value 0.0177497), miR-206 (FC in plasma 2.363, q-value 0.0236391; FC in tissue 1.8331, q-value 0.0754151), miR-214-3p (FC in plasma 4.306, q-value 0.0155355; FC in tissue 1.2490, q-value 0.0001039), and downregulation of, miR-221 (FC in plasma -2.007, q-value 0.0153876; FC in tissue -1.5874, q-value 0.0001039), miR-222 (FC in plasma -1.785, q-value 0.0467997; FC in tissue -1.0827, q-value 0.0170391), in HF samples compared to controls.
Conclusions: Distinct differences in myocardial and plasma miRNA profiles develop in patients with advanced HF compared to controls with a subset of miRNAs exhibiting the same changes in both compartments. Circulating miRNAs might be a novel family of biomarkers in patients with advanced HF reflecting disease severity and progression.
- © 2012 by American Heart Association, Inc.