Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features

Abstract

Epicardial adipose tissue is an unusual visceral fat depot with anatomical and functional contiguity to the myocardium and coronary arteries. Under physiological conditions, epicardial adipose tissue displays biochemical, mechanical and thermogenic cardioprotective properties. Under pathological circumstances, epicardial fat can locally affect the heart and coronary arteries through vasocrine or paracrine secretion of proinflammatory cytokines. What influences this equilibrium remains unclear. Improved local vascularization, weight loss, and targeted pharmaceutical interventions could help to return epicardial fat to its physiological role. This review focuses on the emerging physiological and pathophysiological aspects of the epicardial fat and its numerous and innovative clinical applications. Particular emphasis is placed on the paracrine/endocrine properties of epicardial fat and its role in the development and progression of atherosclerosis.

Figure 1

Microscopic imaging of human epicardial fat. (a) Microscopic appearance of the epicardial layer in the left ventricle. (b) Microscopic appearance of the epicardial layer in the right ventricle. The arrow shows the isles of mature adipocytes. No fascial structure divides the epicardial adipose tissue from the underlying myocardium. Mature adipocytes are more frequent in the right-hand side than the left and can be seen within the subepicardiac myocardium. Scale bar, 1 mm. Figures modified from a previous version published in Iacobellis, G. et al. (2005) Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat. Clin. Pract. Cardiovasc. Med. 2, 536–543, Nature Publishing Group, with permission from the publisher.

Figure 2

Potential physiological, pathophysiological mechanisms and vasocrine/paracrine pathways of epicardial fat. (a) Possible physiological roles attributed to the epicardial fat: release of FFAs as energy to the myocardium in condition of high metabolic demand; expression of the thermogenic protein UCP-1 in response of cold exposure; expression and secretion of cardioprotective factors in conditions of normal coronary and local circulation. (b) Putative mechanisms by which adipokines might reach the coronary artery lumen from the epicardial fat. Adipokines from periadventitial epicardial fat could traverse the coronary wall by diffusion from outside to inside, via a paracrine mechanism. Adipokines might also be released from epicardial tissue directly into the vasa vasorum and be transported downstream into the arterial wall via a vasocrine mechanism. (c) Putative pathophysiological role of epicardial fat in CAD: proinflammatory cytokines are highly expressed and secreted into the coronary lumen; anti-inflammatory adipokines are thought to be downregulated. In high-risk subjects, as well as those with metabolic syndrome and excessive visceral fat accumulation, epicardial fat increases in size and cellularity, exhibiting an elevated number of macrophages.