# Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
## 3 Genomics and Transcriptomics of EAT
Moreover, the expression of EAT UCP-1 and two other thermogenic genes, peroxisome proliferatorator-activated receptor gamma coactivator 1-alpha (PGC1\(\alpha\)) and PR-domain-missing 16 (PRDM16), was down-regulated in patients with reduced ejection-fraction heart failure relative to those with preserved ejection fraction [41]. More unique features add to this unique transcriptome of EAT [21], like an increased fatty acid release [42] and metabolism capacity [43] or the systemic effect on lipid metabolism generated by a high UCP-1 mRNA expression in EAT [44]. Regarding the link between EAT and atherosclerosis, a recent study profiled miRNA for atherosclerosis and discovered among the 250 differently expressed miRNA in EAT from CAD patients an up-regulation of miR-200b-3p. This overexpression is related to oxidative stress, which seems to target histone deacetylase 4 (HDAC4) inhibition and promote endothelial cell damage [45]. HDAC4 is an important regulator of gene expression and participates in the apoptosis process of various cells [46]. The same study supports the hypothesis that EAT accelerates the progression of atherosclerosis by reporting the upregulation of several pro-inflammatory miRNAs (e.g., miR155-3p, miR-206, miR-146a-5p) and the downregulation of anti-inflammatory miRNAs (e.g., Let-7i, miR-127-5p) [45]. [PERSON] et al. have shown that mRNA levels and protein expression of protective adiponectin and adrenomedullin are lower in patients with CAD than in control subjects. However, when comparing plasma adrenomedullin in the left coronary artery with levels in the coronary sinus, the values were not statistically significant, suggesting that EAT may not be responsible for adrenomedullin secretion into the coronary lumen [47]. Omentin-1 is another anti-inflammatory adipokine which is highly expressed in EAT [21; 48] and its supplementation has promising results in reducing atherosclerotic plaque [49]. However, even if circulating omentin-1 levels are lower in CAD, a recent study demonstrated similar results for mRNA omentin levels in the EAT of CAD and non-CAD subjects, suggesting no change in gene expression during the progression of the pathology. Moreover, the proinflammatory adipokine FABP4, which is also secreted by EAT, presented a down-regulated expression in CAD, but only when obesity was present [50]. EAT is also studied in metabolic diseases, particularly diabetes, a multifaceted condition associated with cardiovascular outcomes. EAT samples among diabetic and non-diabetic subjects showed a pronounced alteration of genes associated with inflammatory response and cytokine activity in diabetic patients: IL-1, CD274, PDCD1, ITGAX, PRDM1, LAG3, TNFRSF18, CCL20, IL1 RN and SPP1 [51]. Considering that EAT is a source of inflammatory mediators and cytokines in patients at high risk of heart disease [13; 52], this might be a pathway through which diabetes accelerates CAD development. A possible target for reducing cardiovascular inflammation could be IL-1\(\beta\), since it was the most significant hub gene in diabetic EAT [51]. Another suggested pathway is related to an overexpressed AGE-RACE (advanced glycation end-products receptor advanced glycation end-products) pathway that generates upregulated transcription factors, like NF-kB and FOSL. The increase in these factors is correlated with a higher diabetic EAT gene expression in the innate immune response when compared to the subcutaneous adipose tissue (SAT) transcriptome. In addition, the SAT gene profile is similar in patients with diabetes and those without, suggesting that EAT changes could indeed be representative of diabetes as an important risk factor for CVD [53]. The expression of EAT key genes linked to diabetes mellitus, as a common associated pathology for CVD, is presented in Table 1.