# Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
## 4 Proteomic Insights of EAT  
The proteome governs cellular function and provides valuable insights into disease mechanisms. In contrast to the genome, the proteome provides a more direct connection to the disease phenotype, offering a more precise perspective on disease initialization and progression. There are few proteomic studies performed on EAT and the relationship between EAT proteome and CVD needs further clarification. [PERSON] et al. compared EAT and SAT proteome of patients undergoing heart surgery and concluded that EAT is associated with myocardial stress, since oxidative stress proteins (catalase, glutathione \(S\)-transferase P, protein disulfide isomerase, and phosphoglycerate mutase 1) were more expressed in EAT than SAT of patients with CAD [83]. In atrial fibrillation, myeloperoxidase presented the highest protein levels expressed by the EAT secretome as compared to subjects without atrial fibrillation, together with gene-set neutrophil degranulation. These molecules seem to be involved in structural remodelling, since they aggregate into fibrofatty infiltrates within the atrial myocardium. Moreover, EAT myeloperoxidase presented high expression levels in patients that had no atrial fibrillation at baseline but developed it afterwards, even if there were no differences in cardiovascular risk factors initially between the two groups [84]. By secreting the adipofibokine Activin A, the secretome of EAT facilitates fibrosis of the atrial myocardium [85]. Moreover, proteins responsible for extracellular matrix organization were increased in EAT of ischemic cardiomyopathy patients, suggesting pathologic remodelling [86]. Patients with ischemic cardiomyopathy reveals a distinct EAT proteome from healthy subjects, with a total of 165 proteins significantly changed. These proteins are mainly involved in cytoskeleton organization, cellular metabolism, and immune response [86]. There is also a different EAT proteome in patients who later develop POAF, with low expression levels of a protein associated with maintaining the sinus rhythm, gelsolin. This protein exerts an important role in inflammation and ion channel regulation pathways. At the same time, a favourable effect was expressed by antioxidant enzymes catalase and selenium binding protein-1 (SBP-1), which were up-regulated in the group with POAF [87]. The balance between these proteins and their effect on myocardium processes needs further clarification, since the onset of POAF is linked to an increase in inflammatory and thrombotic proteins in EAT, alongside a decrease in cardioprotective proteins exhibiting anti-inflammatory and anti-lipotoxic properties [88]. Another proteomic study focused on patients with heart failure and demonstrated that serine proteinase inhibitor A3 (Serpina3) was up-regulated in EAT of patients with heart failure vs. the control group (4.63 HF/non-HF ratio). Plasma levels of Serpina3 were elevated in the group with HF compared to the non-HF cohort. Even though this protein exerts an important role in the inflammatory response pathway, there were no plasma changes in immunity markers. However, high levels of Serpina3 were associated with high BNP, ESR and CRP levels [89]. A recent study characterized the cardiac visceral adipose tissue proteome between lean and obese rats. Even though it was not a study that targeted only EAT, but also pericardial and pericoronary adipose tissue, the results highlight an up-regulated expression of UCP-1 protein in lean rats as a marker of brown adipose tissue [90]. However, rodents are not a suitable model for studies on EAT, since persistent disparities exist in the biology of brown fat between mice and humans, and, notably, fat accumulation in rodents frequently occurs outside the pericardium [91]. A proteomic study performed on human EAT does not report differences in UCP-1 expression levels between lean and obese subjects, even if it confirms the fact that EAT is richer in UCP-1 than SAT.