Analysis of mRNA and microRNA profiles in ischemic cardiomyopathy with LVAD support

Cardiac remodeling after myocardial infarction is common, and recovery from end stage ischemic cardiomyopathy (ICM) with left ventricular assist device (LVAD) therapy remains rare. Our goal was to identify micro-RNAs (miRNAs) associated with ICM and to evaluate responses to LVAD therapy to better understand epigenetic mechanisms regulating differential gene expression (DGE).

RNAs were isolated from human myocardial tissues of ICM (n = 11) pre- and post-LVAD placement, along with non-failing (NF) controls (n = 6). Expressions were quantified by utilizing a targeted cardiac panel for mRNA and the nCounter Human v2 miRNA panel for miRNA. Ingenuity pathway analysis (IPA) was performed with DGE. Targeted gene expression profile was validated by performing mRNA-seq.

Compared to NF controls, 33 in pre- and 32 genes in post-LVAD were differentially expressed. IPA of mRNA revealed that signals of inflammatory cytokines and blood pressure disorder were activated in pre-LVAD ICM, and norepinephrine and cells migration were triggered in post-LVAD ICM compared to NF controls. Inflammatory response and apoptosis of cardiomyocytes were inhibited in post compared to pre-LVAD. Relative to NF controls, 195 in pre- and 120 miRNAs in post-LVAD ICM were differentially expressed. IPA of miRNA showed that apoptosis and fibrosis of the heart were stimulated both in pre- and post-LVAD ICM. RNA-seq results validated the targeted gene expression.

In ICM, miRNA expression is linked to apoptosis and fibrosis pathways. These changes persist in post-LVAD therapy and contribute to ongoing changes in mRNA expression associated with Heart failure.