RNA Sequencing Reveals Differentially Expressed Genes in Left Ventricular Biopsies from Ischemic and Dilated Cardiomyopathy Patients

Abstract

Heart failure (HF) affects more than 6 million adults in the U.S and is associated with significant morbidity and mortality. The majority of HF patients suffer from either ischemic (ICM) or dilated (DCM) cardiomyopathy. Little is known about the genetic alterations in DCM or ICM patients. Therefore, our aim was to characterize differentially expressed genes in left ventricular tissue from DCM and ICM patients. Left ventricular tissue of patients with end-stage HF due to ICM (n=6) or DCM (n=7) was collected during implantation of a ventricular assist device (LVAD). Myocardial tissue from patients with septal myectomy during aortic valve surgery (n=6) served as control. Specimens were collected and immediately quick frozen in liquid nitrogen. RNA was purified and quality checked, whereafter PolyA-RNA-Sequencing was performed. For each sample, ∼30 million reads were obtained. Differential gene expression analysis was performed using a false discovery rate (FDR) ≤ 0.1 and log2 count per million (logCPM) ≥ 1. The commercial Ingenuity Pathway Analysis (IPA, www.qiagen.com/ingenuity) software was used to determine significantly affected pathways and molecular networks. RNA-sequencing revealed 300 differentially expressed genes in DCM vs. control patients, 508 genes in ICM vs. control patients, and 28 genes in DCM vs. ICM patients. Ingenuity pathway analysis (IPA) showed alterations of different pathways in DCM vs. ICM patients, with many downregulated pathways in DCM patients and many upregulated pathways in ICM patients. The present data suggest that different genes and pathways are involved in the underlying pathomechanisms of ICM and DCM. Further research in this field is needed and could reveal potential new diagnostic and therapeutic targets.