Micro Rna Expression Of Heart Failure Patients And Responses To Left Ventricular Assistant Device Support

Purpose Micro RNAs are key regulators of various biological processes including the pathogenesis of heart failure (HF). In this study we compared miRNA profiles of heart failure (HF), left ventricular assist devices (LVAD) and non-failing (NF) hearts patients. Our goal was to identify epigenetic mechanisms involved in HF and responses to LVAD therapy. Methods RNAs were isolated from myocardial tissues of HF patients without mechanical support at the time of transplant (n=6) and after LVAD (n=6) placement in non-ischemic dilated cardiomyopathy patients along with NF controls (n = 6). NanoString analysis was used to compare miRNA expression among in HF, LVAD, and control patients. NanoString miRNA raw count data were preprocessed and normalized using nSolver 4.0 Analysis Software. Ingenuity Pathway Analysis (IPA) was carried out on differentially expressed micro RNA to understand the biological pathways involved. Results Our sample population was 84% male with an average age of 57 and 82% Caucasian, 16% African American and 2% Asian. Forty four miRNAs were differentially expressed in HF patients than NF control and 79 miRNAs were differentially expressed in HF patients when compared to post-LVAD HF patients. IPA analysis revealed that heart enlargement was significantly altered in HF compared to NF control with p value of 2.58E-04. Three miRNA were upregulated (mir590-5p, mir146a-5p and mir-761-5p) and three were downregulated by more than two folds (mir-1, mir-23a-3p and mir497-5). Heart enlargement was also significantly different in pre vs post with p value of 2.57E-02. Five miRNAs were involved with four upregulated (mir-590-5p, mir146a-5p, mir-761 and mir 140-3p) while only one was downregulated (mir-497-5p). Conclusion End stage heart failure is characterized by cardiac remodeling, arrhythmias, fibrosis and a decline in myocyte contractility. Our results identify a large number of miRNAs that are associated with end stage heart failure and cardiac enlargement in addition to the miRNAs associated with remodeling on LVAD therapy. Micro RNA profiles can identify molecular mechanisms of disease and serve as potential biomarkers or therapeutic targets.