# Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
## 3 Genomics and Transcriptomics of EAT
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Gene/Product Name** & \begin{tabular}{c} **mRNA Expression in** \\ **Diabetic EAT vs.** \\ **Non-Diabetic EAT** \\ \end{tabular} & \begin{tabular}{c} **Biological Process** \\ \end{tabular} & \begin{tabular}{c} **Reference** \\ \end{tabular} \\ \hline IL-lb (interleukin-1 beta) & Up-regulated & \begin{tabular}{c} positive regulation of MAP kinase \\ activity, cytokine activity, positive \\ regulation of canonical NF-kappaB \\ signal transduction \\ \end{tabular} \\ \hline CD274 (programmed cell death 1 ligand 1) & Up-regulated & \begin{tabular}{c} regulation of activated CD4-positive, \\ alpha-beta T cell apoptotic process, \\ transcription coactivator activity \\ \end{tabular} \\ \hline PDCD1 (programmed cell death protein 1) & Up-regulated & \begin{tabular}{c} programmed cell death protein 1 \\ \end{tabular} \\ \hline ITGAX (integrin alpha-X) & Up-regulated & \begin{tabular}{c} receptor tyrosine kinase binding, \\ integrin binding, cell adhesion \\ \end{tabular} \\ \hline PRDM1 (PR domain zinc finger protein 1) & Up-regulated & \begin{tabular}{c} DNA-binding transcription repressor \\ activity, RNA polymerase II-specific \\ \end{tabular} & [PERSON], et al. [51] \\ \hline LAG3 (lymphocyte activating 3) & Up-regulated & \begin{tabular}{c} adaptive immune response, negative \\ regulation of interleukin-2 production, \\ cell surface receptor signalling pathway \\ \end{tabular} \\ \hline TNFRSF18 (TNF receptor superfamily member 18) & Up-regulated & \begin{tabular}{c} tumour necrosis factor-mediated \\ signalling pathway, positive regulation \\ of cell adhesion, negative regulation of \\ apoptotic process \\ \end{tabular} \\ \hline CCL20 (C-C motif chemokine 20) & Up-regulated & \begin{tabular}{c} chemotaxis, immune response, positive \\ regulation of T cell migration \\ \end{tabular} \\ \hline IL1 RN (interleukin-1 receptor antagonist protein) & Up-regulated & \
\begin{tabular}{c} lipid metabolic process, immune \\ response, cytokine activity \\ \end{tabular} \\ \hline SPP1 (osteopontin) & Up-regulated &
\begin{tabular}{c} cytokine activity, integrin binding \\ \end{tabular} \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Expression of EAT key genes linked to diabetes mellitus. A comparison of EAT and visceral adipose tissue depots from the abdomen show a clearly distinct gene expression signature. At a rigorous \(p\) value (<1.1 \(\times\) 10\({}^{-6}\)) COL4A4 and HBM presented high expression levels in EAT compared to visceral samples [21], emphasizing the importance of pathways like extracellular matrix remodelling, immune signalling, beigening, thrombosis, and coagulation [48]. Moreover, there is evidence that specific transcriptomic signatures of EAT depend on the pericoronary, periatrial, or periventricular anatomical location (Figure 1). Interestingly, periventricular, and not pericoronary EAT, is the most proinflammatory depot at the gene expression level. However, peri-coronary EAT remains more involved in the process of atherosclerosis [21], since it associates with the sphingolipid metabolism pathway and sphingolipids promote the retention of oxidized LDL, favouring the formation of atherosclerotic plaque [55; 56]. On the other hand, periatrial EAT is involved in atrial fibrillation with up-regulation of genes encoding pro-arrhythmogenic factors, the extracellular matrix structural constituent conferring tensile strength, and also genes involved in cardiac muscle contractility and actomyosin structure organization. Considering the limitation of studying EAT only in patients undergoing cardiac surgery, subcutaneous adipose tissue (SAT) was considered a possible second-best option, leading the way to comparison studies between the two tissues. Table 2 documents the expression of key EAT genes involved in CAD, alongside a comparison with their expression level in SAT.