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

Relatively few mRNAs were differentially expressed in ICM myocardium versus non-failing controls, both before and after LVAD placement.

• Myocardial tissue was from ICM patients (n = 11) pre- and post-LVAD and non-failing (NF) controls (n = 6).
• Compared to NF controls, 33 genes in pre-LVAD and 32 genes in post-LVAD tissue were differentially expressed.
• mRNA was quantified using a targeted cardiac gene panel.

Pathway analysis of mRNA showed inflammatory cytokine and blood pressure disorder signals activated in pre-LVAD ICM, while norepinephrine and cell migration signals were triggered post-LVAD, relative to NF controls.

• Ingenuity pathway analysis (IPA) was applied to the differentially expressed genes.
• Pre-LVAD ICM vs NF: activation of inflammatory cytokines and blood pressure disorder signaling.
• Post-LVAD ICM vs NF: activation of norepinephrine and cell migration signaling.

Inflammatory response and cardiomyocyte apoptosis were inhibited in post-LVAD compared with pre-LVAD ICM tissue at the mRNA level.

• This comparison was based on IPA of mRNA differential expression between post- and pre-LVAD samples.
• The findings suggest some LVAD-associated reversal of mRNA-level pathology.

A large number of miRNAs were differentially expressed in ICM compared with NF controls, with fewer after LVAD support.

• 195 miRNAs were differentially expressed in pre-LVAD ICM and 120 in post-LVAD ICM relative to NF controls.
• miRNAs were quantified with the nCounter Human v2 miRNA panel.

miRNA pathway analysis indicated that apoptosis and fibrosis of the heart were stimulated in both pre- and post-LVAD ICM.

• IPA of differentially expressed miRNAs was compared with NF controls.
• These pathway signals persisted after LVAD therapy, unlike the mRNA-level inhibition of inflammation and apoptosis.

mRNA-seq validated the targeted gene expression profile.

• The targeted cardiac panel results were cross-checked with mRNA-seq.
• The abstract reports that RNA-seq results validated the targeted gene expression.

The authors conclude that miRNA-linked apoptosis and fibrosis changes persist after LVAD therapy and contribute to ongoing mRNA expression changes associated with heart failure.

• This may help explain why recovery from end-stage ICM with LVAD is rare.
• The study aimed to understand epigenetic mechanisms regulating differential gene expression.