Differential Expression of Cardiac Fat Long Non‐Coding RNAs in Coronary Artery Disease

Abstract

Coronary artery disease (CAD) is characterized by the buildup of atherosclerotic plaques within the coronary arteries, leading to serious complications. CAD affects 7.2% and 4.2% of males and females, respectively. Epicardial adipose tissue (EAT) interacts with the heart and vasculature, but its mechanistic role in CAD is not completely understood. A more comprehensive view of non‐coding RNA (ncRNA) expression in EAT is needed to better characterize its role in CAD. To conduct this characterization, in an IRB‐approved investigation, we isolated the microRNA (miRNA), long non‐coding RNA (lncRNA), and messenger RNA (mRNA) from the EAT and subcutaneous adipose tissue (SAT) of male and female CAD patients undergoing coronary artery bypass graft as well as from non‐CAD patients undergoing aortic valve replacement. Differential expression of these RNAs between tissues, disease status, and sex was determined using next generation sequencing (mRNA) and microarrays (miRNA and lncRNA). Functional and pathological associations of the differentially expressed RNAs were determined using Ingenuity Pathway Analysis, GO, KEGG, and TAM 2.0. DIANA‐LncBase was used to identify experimentally verified miRNA‐lncRNA interactions. NGS showed differential expression of mRNAs associated with cardiovascular function in EAT but not in SAT. miRNA microarray showed that ncRNA expression within the EAT of CAD patients is distinct from its expression in non‐CAD patients. 14 miRNAs were differentially expressed in EAT from patients with CAD compared to those without CAD. Similarly, lncRNA RT2 PCR array showed a downregulation of three lncRNAs: IPW, TINCR, and linc00853, between the EAT of CAD compared to non‐CAD male patients but not in the EAT of female patients. DIANA‐LncBase showed high confidence pairings of IPW with three miRNAs that were upregulated in the EAT of patients with CAD: hsa‐miR‐24‐3p, hsa‐miR‐26b‐5p, and hsa‐29c‐3p. This suggests that IPW may serve as a ‘sponge’ for these three miRNAs in the EAT of patients without CAD, but its downregulation in CAD reduces that interaction. TAM 2.0 showed these three miRNAs to be associated with functional pathways such as vascular inflammation, apoptosis, adipogenesis, etc. Overall, these findings both reveal potential ncRNA biomarkers for CAD and elucidates possible pathological roles of EAT in CAD mediated by ncRNAs.