Identification of the Expression Patterns of Fatty Acid Oxidation Genes in a Heterogenic Cardiomyopathy Patient Cohort

Abstract

Cardiomyopathy is one of the major causes of heart failure that affects approximately 26 million patients worldwide. In a healthy situation, the heart depends on fatty acid oxidation (FAO) to maintain its energy demand. In failing hearts, the heart reverts to a fetal-like metabolic state in which FAO is downregulated and the heart switches to glucose metabolism. Peroxisome proliferator-activated receptor alpha (PPARA), a regulator of FAO, has recently been found to be hypoacetylated and its downstream effectors downregulated in dilated cardiomyopathy. However, the exact mechanisms remain largely unknown. The main purpose of this internship was to identify the specific FAO expression patterns in a large heterogenic patient cohort and investigate the involvement of PPARA regulation. The secondary goal was to set up a transcriptomic pipeline within Galaxy, a user-friendly bioinformatics platform, and test whether this platform can be used in diagnostics in the future. Differential expression analysis and gene enrichment of RNA-sequencing data show a type-specific FAO expression pattern of DCM and LVH versus HCM and confirm a downregulation of FAO related processes. Public RNA-sequencing data after the use of a bezafibrate, a PPARA agonist, which has been integrated, shows the upregulation of genes that are downregulated in our data. Combined, the results confirm the downregulation of FAO, but indicate a disease-type-specific FAO expression pattern. The results from the Galaxy pipeline show that this pipeline is suitable for transcriptomic analyses. Furthermore, we highlight the potential therapeutic role of bezafibrate in cardiomyopathy.