Epicardial adipose tissue, metabolic disorders, and cardiovascular diseases: recent advances classified by research methodologies

Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy and physiology of the EAT determines its great potential in locally influencing adjacent tissues such as the myocardium and coronary arteries. Classified by research methodologies, this study reviews the latest research progress on the role of EAT in cardiovascular diseases (CVDs), particularly in patients with metabolic disorders. Studies based on imaging techniques demonstrated that increased EAT amount in patients with metabolic disorders is associated with higher risk of CVDs and increased mortality. Then, in-depth profiling studies indicate that remodeled EAT may serve as a local mediator of the deleterious effects of cardiometabolic conditions and plays a crucial role in CVDs. Further, in vitro coculture studies provided preliminary evidence that the paracrine effect of remodeled EAT on adjacent cardiomyocytes can promote the occurrence and progression of CVDs. Considering the important role of EAT in CVDs, targeting EAT might be a potential strategy to reduce cardiovascular risks. Several interventions have been proved effective in reducing EAT amount. Our review provides valuable insights of the relationship between EAT, metabolic disorders, and CVDs, as well as an overview of the methodological constructs of EAT-related studies. Considering the advances in research and biological technology, our understanding of EAT has undergone a continuous deepening process, from volumetric measurement to in-depth profiling of EAT, and from correlational to cause-effect studies. EAT amount measured by imaging techniques is significantly higher in patients with metabolic disorders. An increased EAT volume is associated with a higher risk of developing metabolic syndrome, cardiovascular mortality, atrial fibrillation (AF) incidence, and reduced cardiac function. Further, in-depth profiling studies suggest that EAT is remodeled into a more proinflammatory phenotype in patients with metabolic disorders. The levels of proinflammatory cytokines such as IL-1, IL-6, TNF-alpha, and interferon-gamma in EAT under conditions of metabolic disease are significantly higher than those in the control group. Additionally, the expression of scavenger receptors (SRs) and macrophage infiltration are at higher levels. Finally, coculture studies explored the paracrine effect of EAT. Studies found that the secretory profile of EAT form patients with metabolic disorders is distinct from the control group. Moreover, in vitro coculture studies, in which cardiomyocytes were cultured with secretory products of EAT biopsies from patients, have shown that secretory products of EAT from patients with metabolic disorders exhibited detrimental effects on cardiomyocytes, such as impairing the contractile function of cardiomyocytes. Furthermore, coculture of the cardiomyocytes with secretory products of EAT from AF patients resulted in changes in cardiomyocyte electrophysiology and increased cardiac fibrosis, which are related to the mechanisms underlying AF.#image