# Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
## 4 Proteomic Insights of EAT
However, results underline a higher expression level of another beige fat marker, Slc36a2, in lean subjects compared to levels in overweight subjects. Interestingly, when analysing whether expression levels of all the known beige markers (Tmem26, Slc36a2, Trnfsr9, Tbx1, P2 rx5) clustered with UCP-1 are modified in obesity, no significant difference was observed. However, in the case of CAD, this cluster was down-regulated. The same study reported a positive association of EAT thermogenic markers with plasma HDL-cholesterol and a negative association withcirculating TG, confirming the important role it has in lipid metabolism [92]. However, ABCA1 gene expression in EAT decreases, suggesting an impairment in reverse cholesterol transport process [93]. A systematic review of the literature concerning dysregulated proteins emphasizes the role EAT has in CAD physiopathology. The immune system triggers pathways linked to elevated levels of secreted proteins, whereas pathways associated with the binding and uptake of ligands by scavenger receptors were correlated with low levels of secreted protein. These results support the cardioprotective effects of physiological EAT via the paracrine or vasocrine secretion of anti-inflammatory adipokines. Simultaneously, they highlight the shift in the epicardial fat secretome equilibrium when adipocyte dysfunction occurs, resulting in the release of proinflammatory adipokines from epicardial adipocytes [94; 95]. Patients with CAD also present high levels of MMP-9 expression in EAT, suggesting vascular remodelling processes and vascular smooth muscle migration [96]. Meanwhile, clusterin, a molecule recognized for its cardioprotective effects against ischemia and necrosis, demonstrates upregulated EAT expression according to proteomic data, which aligns with increased plasma levels observed in studies [96; 97]. The EAT proteome was also studied in patients with HFpEF, identifying 96 proteins (71 upregulated and 25 downregulated) differentially expressed from the group of patients without the pathology. The results suggest that these proteins (such as CD36, POSTN, and TRAP1) play a predominant role in HFpEF, encompassing lipid metabolic disorder, inflammation, and mitochondrial dysfunction [98]. Another study that compared the group with HFpEF with the group with heart failure with reduced ejection fraction (HFrEF) identified TGM2 as a possible new marker for discriminating between the two diseases. There is insufficient evidence to suggest this protein is secreted by EAT and then released into the circulation, but TGM2 is decreased in EAT and also in the plasma of patients with HFrEF, suggesting a poorer prognosis for HFrEF. TGM2 is a calcium-dependent acyltransferase involved in the progression of heart failure with an important role in stiffening the extracellular matrix and contractility of the myocardium [99]. GLO1 emerges as a distinguishing protein for increased EAT thickness, associated with oxidative stress and implicated in heart failure differentiation. Conversely, MMP-2 shows a negative association with EAT thickness, previously linked to myocardial fibrosis in coronary bypass-surgery patients and atrial fibrillation. Additionally, lower levels of vascular endothelial growth factor-D were observed in patients with increased EAT thickness, hinting at endothelial dysfunction as a component in HFpEF disease development [100].