Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

Abstract

Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFkappaB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

Epicardial adipose tissue: at the heart of the obesity complications

“…The association between EAT and CAD from a pathophysiologic perspective This epidemiological and experimental evidence together with histopathological data showing the presence of dense inflammatory infiltrates, mainly represented by macrophages, lymphocytes and mast cells, in EAT of CAD patients [41,42], is the basis for the hypothesis that EAT might locally and detrimentally contribute to coronary atherogenesis.…”

“…Innate immunity can be activated within EAT by Tolllike receptors (TLRs) binding, with consequent nuclear factor-kappaB (NFkappaB) translocation into the nucleus inflammatory mediators transcription [42]. As such, EAT sampled from subjects with CAD showed higher NFkappaB, c-Jun N-terminal kinase (JNK) activity, TLR-2 and TLR-4 expression levels, all indicative of macrophage recruitment and activation [42].…”

“…As such, EAT sampled from subjects with CAD showed higher NFkappaB, c-Jun N-terminal kinase (JNK) activity, TLR-2 and TLR-4 expression levels, all indicative of macrophage recruitment and activation [42]. Of interest, a recent study using next-generation sequencing technologies demonstrated the presence of bacterial DNA into EAT surrounding diseased coronary arteries, suggesting that EAT is susceptible to microbial colonization that might, thereby, contribute to elicit a proinflammatory response [43].…”

Thermogenic potential and physiological relevance of human epicardial adipose tissue

“…However, a direct microcirculatory interconnection between the two has not been established so far. 23,24 Nonetheless, owing to its unique anatomic juxtaposition, numerous plausible physiological roles have been offered to epicardial fat including, but not limited to, that (1) it serves as the anatomic site for the cardiac nervous system, 25 (2) it serves to cushion the coronary arteries against pulse wave torsion, 14 (3) it serves as a heating blanket to protect the myocardium during hypothermia, 26,27 (4) it is an immunological tissue that serves to protect the myocardium and coronaries against pathogens and inflammatory activators 28 and (5) it serves to maintain fatty acid homeostasis in the coronary microcirculation. 5 In a seminal study looking at the anatomy, histology and biochemical properties of epicardial fat across a spectrum of species, epicardial fat was reported to exhibit a higher capacity for breakdown, synthesis and release of fatty acids relative to other intra-abdominal fat depots in guinea pigs.…”

“…51 A potential role of nuclear factor-κB and c-Jun N-terminal kinase pathways in the enhancement of inflammation observed in epicardial fat under CAD conditions has also been proposed. 2 In addition, higher oxidative stress levels, including reactive oxygen species production and higher levels of enzymes involved in regulating oxidative stress such as catalase and glutathione S-transferase P, have been reported in epicardial fat relative to subcutaneous fat in patients with CAD. 52 In addition to the studies looking at gene expression of the inflammatory and oxidative stress markers, proteomic and secretome analyses of epicardial fat obtained from CAD patients have also revealed that it is capable of secreting factors that can induce atherogenic changes in monocytes and endothelial cells, 53 as well as induce cardiomyocyte dysfunction.…”