Investigating interactions between epicardial adipose tissue and cardiac myocytes: what can we learn from different approaches?

Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies would be beneficial. Recently it has become apparent that epicardial adipose tissue plays an important role in normal and pathological cardiac function, and it is now the focus of considerable research. Epicardial adipose tissue can be studied by imaging of various kinds, and these approaches have yielded much useful information. However at a molecular level it is more difficult to study as it is relatively scarce in animal models and, for practical and ethical reasons, not always available in sufficient quantities from patients. What is needed is a robust model system in which the interactions between epicardial adipocytes and cardiac myocytes can be studied, and physiologically relevant manipulations performed. There are drawbacks to conventional culture methods, not least the difficulty of culturing both cardiac myocytes and adipocytes, each of which has special requirements. We discuss the benefits of a three-dimensional co-culture model in which in vivo interactions can be replicated

Coronary Artery Disease and Epicardial Adipose Tissue

Epicardial adipose tissue (EAT) can locally affect the coronary arteries and play a significant role in the development and progression of coronary artery disease (CAD), as emerged only recently. The mechanisms through which epicardial fat can cause atherosclerosis are complex and multifactorial. Its anatomical proximity to the heart, the unique transcriptome, and intense proteasome are the major atherogenic factors of the epicardial adipose tissue. EAT can cause atherosclerosis via several mechanisms that could be summarized in inflammation, innate immunity, oxidative stress, lipotoxicity, and glucotoxicity. EAT, regardless of whether it is measured as volume or thickness, is higher in patients with CAD as compared to individuals without CAD. The more proximal EAT is to the coronary arteries, the higher is its inflammatory activity. EAT provides prognostic information and improves the prediction of first coronary events. EAT volume is greater in subjects with incident coronary heart disease. The incidence of fatal or nonfatal coronary event significantly increased with higher EAT and remains significant even after adjustment for coronary calcium calcification score and obesity. EAT is linked to early coronary plaque components and, therefore, plays a role in the early phases of asymptomatic atherosclerosis. Routine assessment of EAT could be implemented for a better prediction and stratification of CAD

Transcriptomic and Proteomic Analysis of the Epicardial Adipose Tissue

The study of epicardial adipose tissue (EAT) has been limited by its accessibility due to its proximity to the heart. Moreover, many common animal models do not have EAT, leaving its functional role underestimated and poorly elucidated. Recent advances in medicine and science have allowed for better studies that provide a more comprehensive understanding of its physiological role. One way to dissect its function is the study of its gene expression. In this chapter, we summarize transcriptomic and proteomic analyses which show that EAT expresses a unique set of genes setting it apart from other adipose tissues in the body. This distinctive set of genes modulates a feedback mechanism that has direct interaction with the myocardium. The EAT shares its blood supply with the coronary arteries and innervation with the cardiac muscle, provides physical protection, and regulates energetic metabolites needed by the myocardium. Transcriptomic and proteomic studies show that it is a local source of adipokines with paracrine influence on the myocardium due to the intimate microcirculation shared by both tissues. These analyses also show that it has a role in the immune and endocrine systems affecting the rest of the body. Furthermore, regulation of EAT gene expression is not monolithic and can be affected by multiple factors such as sex, age, underling disease, medication, etc. Gene expression studies can therefore provide great insight into the function of EAT and its role in health and disease