Epicardial Fat: Physiological, Pathological, and Therapeutic Implications

Abstract

Epicardial fat is closely related to blood supply vessels, both anatomically and functionally, which is why any change in this adipose tissue's behavior is considered a potential risk factor for cardiovascular disease development. When proinflammatory adipokines are released from the epicardial fat, this can lead to a decrease in insulin sensitivity, low adiponectin production, and an increased proliferation of vascular smooth muscle cells. These adipokines move from one compartment to another by either transcellular passing or diffusion, thus having the ability to regulate cardiac muscle activity, a phenomenon called vasocrine regulation. The participation of these adipokines generates a state of persistent vasoconstriction, increased stiffness, and weakening of the coronary wall, consequently contributing to the formation of atherosclerotic plaques. Therefore, epicardial adipose tissue thickening should be considered a risk factor in the development of cardiovascular disease, a potential therapeutic target for cardiovascular pathology and a molecular point of contact for "endocrine-cardiology."

Figure 1

EAT secretion mechanism. Adipokines entering the wall by a “vasocrine” mechanism (a) using as transportation vasa vasorum or using a paracrine mechanism (b), which through dissemination adipokines pass down the gradient of concentration. The molecules continue to step up to the deeper layers of blood vessels (endothelial and muscular) which trigger several effects. EAT: epicardial adipose tissue, TNF-α: tumoral necrosis factor alpha, and IL-6: interleukin 6.

Figure 2

Mechanism of action of insulin in the endothelial cell. The interaction of insulin with its receptor results in autophosphorylation of tyrosine residues and heterophosphorylation of second messengers such as IRS-1, which phosphorylates PI3K, leading to the activation of a cascade of phosphorylation ending with expression of various physiological effects, like the production of endothelial NO. IRS-1: insulin receptor substrate 1, PI3K: phosphatidylinositol 3-kinase, PIP₂: phosphatidylinositol diphosphate, PIP₃: phosphatidylinositol triphosphate, PDK-1: dependent kinase PI3K, Akt: protein kinase B, GLUT-4: glucose transporter 4, and NO: nitric oxide.