Profiling of Non-Coding Regulators and Their Targets in Epicardial Fat from Patients with Coronary Artery Disease

Abstract

Epicardial fat is a continuously growing target of investigation in cardiovascular diseases due to both its anatomical proximity to the heart and coronary circulation and its unique physiology among adipose depots. Previous reports have demonstrated that epicardial fat plays key roles in coronary artery disease, but the non-coding RNA and transcriptomic alterations of epicardial fat in coronary artery disease have not been investigated thoroughly. Micro- and lncRNA microarrays followed by GO-KEGG functional enrichment analysis demonstrated sex-dependent unique mi/lncRNAs altered in human epicardial fat in comparison to subcutaneous fat in both patients with and without coronary artery disease (IRB approved). Among the 14 differentially expressed microRNAs in epicardial fat between patients with and without coronary artery disease, the hsa-miR-320 family was the most highly represented. IPW lncRNA interacted with three of these differentially expressed miRNAs. Next-generation sequencing and pathway enrichment analysis identified six unique mRNAs–miRNA pairs. Pathway enrichment identified inflammation, adipogenesis, and cardiomyocyte apoptosis as the most represented functions altered by the mi/lncRNAs and atherosclerosis and myocardial infarction among the highest cardiovascular pathologies associated with them. Overall, the epicardial fat in patients with coronary artery disease has a unique mi/lncRNA profile which is sex-dependent and has potential implications for regulating cardiac function.