# Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape
## 2 Biological and Pathophysiological Relevance of EAT  
EAT is located between the myocardium and the visceral epicardium and is different from pericardial adipose tissue, which is located on the external surface of the parietal pericardium [15]. These two types of adipose tissue surrounding the heart should not be confused as they present differences in terms of embryogenic origin, blood supply and metabolic properties [14; 16]. Even though both have important roles, EAT has gained more interest over the years since clear evidence has shown its role as an active endocrine organ, serving as a source of several bioactive molecules [17]. Moreover, EAT has a unique characteristic: it is the only visceral fat depot that comes in direct contact with the target organ, with no muscle fascia separating them. This allows crosstalk between EAT and the myocardium, also describing a shared microcirculation [2]. Therefore, the lack of a barrier reveals interaction mechanisms (paracrine and vasocrine) that exert effects on the myocardium and coronary vasculature by expressing various cytokines [17]. These effects can be protective or harmful and are the results of various molecules with the following properties: proinflammatory/proatherogenic (MCP-1, TNF-\(\alpha\), and interleukines), anti-inflammatory/anti-atherogenic (adiponectin and adrenomedullin), thermogenic (UCP 1), insulin-mimetic (resistin, visfatin and omentin), brown fat differentiation transcription factors (PRDM16 and PGC-1\(\alpha\)), vascular remodelling, blood pressure control, and adipogenesis or myocardial hypertrophy factors (angiotensin, angiotensin, and leptin) [18]. The hypothesis that EAT may play an active role in heart disease is still under debate, with recent publications reporting multiple correlations between these molecules and heart physiopathology, but they are still not proven to be cause-related. Whether beneficial in lean subjects or detrimental when in excess, EAT presents a high association with CVDs [19; 20]. In normal physiological states, EAT constitutes around 20% of the total heart mass. The distribution is different around the heart and, moreover, each regional EAT depot has different effects as a result of its own transcriptome and proteome [21]. EAT serves not only as an energy reservoir, but also as an endocrine organ that plays a crucial role in regulating heart homeostasis. Besides vasocrine and paracrine interaction mechanisms between EAT and the myocardium, extracellular vesicles (EVs) containing microRNAs serve as novel means of communication. EAT-secreted vasoactive products facilitate free fatty acid influx assuring energy to heart cells, while fatty-acid-binding protein-4 (FABP-4), expressed by EAT, may contribute to intracellular free fatty acid transport from EAT to the myocardium [22]. Clinical studies have reported high EAT volume in patients with metabolic syndrome [23], although EAT density might be a better predictor of cardiometabolic risk [24]. Furthermore, EAT volume appears to be an autonomous predictor of diabetes in patients with coronary artery disease (CAD) who are already undergoing treatment for elevated cholesterol values [25]. Thus, while statins have been suggested as potential EAT modulators [26; 27], this hypothesis still requires validation. Multiple studies robustly support the role of EAT in CVDs including atherosclerosis, arrhythmias, aortic stenosis, thromboembolism, and heart failure. High EAT thickness correlates with slow coronary flow, serving as a predictive indicator for the presence of subclinical atherosclerosis [28], while also affecting the stability of the plaque in the coronary artery [29] and possibly exerting a systemic influence on the progression of atherosclerosis [30]. A prospective study on 4093 participants followed for approximatively 8 years reported an increase in fatal and non-fatal coronary events, together with EAT thickness, independent of cardiovascular risk factors [31].