Abstract 17364: Deep-Sequencing of Circulating microRNAs Reveals Distinct Profiles in Patients with Advanced Heart Failure and Specific Dynamics Following Mechanical Unloading
Background: No data exist on the time course of circulating microRNA (miRNA) profiles in patients with heart failure (HF) before and after mechanical support initiation. We performed miRNA profiling using deep sequencing on plasma samples from patients with advanced HF at the time of left ventricular assist device (LVAD) implantation, at 3 and 6 months follow-up and healthy controls.
Methods: Total RNA was isolated by a modified TRIzol protocol from 5 controls matched to 5 adults with HF and at 3 and 6 months follow-up post-LVAD (3 ischemic cardiomyopathy, 2 dilated cardiomyopathy). Multiplexed small RNA libraries were sequenced on the Illumina HiSeq 2000 and analyzed using an in-house annotation pipeline, differential expression was done by fitting a negative binomial model and using an adjusted p-value of 0.05 (Benjamini-Hochberg).
Results: 44,695,589 reads of which 26,106,582 represented miRNAs were obtained. Unsupervised hierarchical clustering separated samples into two groups: 1) samples at implantation (decompensated HF) and 2) healthy controls together with the 3 and 6 months follow-up patients. When comparing samples at time of implant to healthy controls, 76 miRNAs were differentially regulated (q-value < 0.05). Of note, miR-208a/b, miR-195, miR-499, miR-1 (implicated in cardiac hypertrophy, cardiac dysfunction, and alterations in conduction, respectively) were upregulated and miR-199a (hypoxia-induced apoptosis) was downregulated. At 3 and 6 months follow-up, none of the miRNAs demonstrated significant differences compared to controls. When comparing samples at implantation to controls, 3 and 6 months follow-up samples, 270 miRNAs demonstrated significant differences. Again, miR-208a/b, miR-195, miR-499 and miR-1 (q-values 6.5e-20 to 4.6e-9) were upregulated at time of implant while miR-199a (q-value=4.7e-9) was downregulated.
Conclusions: Mechanical unloading through LVAD appears to correct altered miRNA profiles in patients with HF within the first 3 months after implantation with sustained corrective changes through 6 months of follow-up. Circulating miRNA profiles allow the characterization of cardiac-specific miRNAs in patients with advanced HF and during the course of mechanical unloading through LVAD support.
- © 2012 by American Heart Association, Inc.