Abstract 18821: Plasma MicroRNA Sequencing Reveals Novel MicroRNA Biomarkers of Systolic Heart Failure
Introduction: Plasma microRNAs (miRs) are RNA molecules that regulate messenger RNA transcription. MiRs are remarkably stable in the plasma and select miRs have been demonstrated to be useful biomarkers in heart failure (HF).
Hypothesis: We hypothesized that levels of plasma miRs can be identified that accurately diagnose and predict outcomes in heart failure patients.
Methods: Our cohort consisted of 30 participants with advanced systolic HF and 36 age and gender-matched controls with no history of hypertension or cardiovascular disease. Plasma was isolated from venous blood samples. Using a quantitative nuclease protection assay coupled with next generation sequencing, we sequenced 2,256 miRs annotated in miRBASE v20 on the Illumina platform. The sequence data was standardized and normalized to account for counts below the limit of detection. Differentially regulated miRs were analyzed with the DIANA miRpath and KEGG pathway analysis tools.
Results: Twenty-seven miRs were identified that were differentially regulated between the HF patients and controls with a corrected p-value of < 0.001 and fold-change > +/- 2. Ten miRs were up-regulated and 17 miRs were down-regulated. Many of the miRs (miR- 484, miR-3178, miR- 5096) have not been previously been described in HF patients. Pathway analysis revealed miR involvement in cell cycle control, TGF-β signaling, fibrosis, Akt signaling, apoptosis and hypertrophy. We used these results to create a panel of 12 miRs was created (t-test p-value < 1.0*10-12) that had the ability to distinguish between HF and controls with an area under the curve of 0.96, p = 3.8*10-8. The sensitivity and specificity of this panel as a biomarker of HF were 97% and 93 %, respectively.
Conclusions: MiRs that were previously not associated with HF were identified and a panel of these miRs may be useful as biomarkers of HF. In addition, these miRNA or a subset may have an important biological function in the mediation of the end-organ dysfunction that typifies advanced systolic HF.
Author Disclosures: P. Shah: None. J. Vockley: None. A. Ulyanov: None. R.K. Iyer: None. S. Phillips: None. T. Vilboux: None. C.O. Connor: None. J. Niederhuber: None.
- © 2016 by American Heart Association, Inc.