Abstract 18324: The Innate Immune System, Nlrp3 Inflammasome is Intensified in Epicardial Adipose Tissue around Coronary Arterial Lesions: Evidence from Biopsied Adipose Tissue in Coronary Artery Bypass Surgery

Abstract

Background: The emergence of chronic inflammation could enhance obesity-induced insulin resistance and atherosclerosis, but the underlying mechanisms remain unclear. The Nod-like receptor (NLR) family of innate immune cell sensors, such as pyrin domain-containing-3 (NLRP3) inflammasome are implicated as one candidate to elicit nonmicrobial originated signals in atherosclerosis. Objectives: We determined association between the NLRP3 inflammasome signals in epicardial adipose tissue (EAT) and coronary atherosclerosis in human.

Method: Pair samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery for coronary (CAD, n=40) or non-coronary artery disease (non-CAD, n=40). Expression of NLRP3 in EAT was analyzed by immunohistochemical staining using antibodies against NLRP3, CD68 and IL18. Expression of pro- and anti-inflammatory adipocytokines in EAT was evaluated by quantitative real-time polymerase chain reaction (qPCR).

Results: By immunohistochemical staining, NLRP3 signals were well detected in EAT of the CAD group, but rarely in EAT of the non-CAD group. The signals was co-localized with macrophages in EAT determined by anti-CD68 or anti-F4/80 immunostaining. By qPCR, signals of NLRp3, TLR1, TLR2, TLR4, but not TLR3, TLR5 and TLR9, were increased in EAT of the CAD group as compared to that of the non-CAD group. Signals of MyD88, but not MD-2, were also enhanced in EAT of the CAD group. Signals of IL-18 and adiponectin were decreased in EAT of the CAD group.

Conclusions: We, for the first time, showed that NLRP3 inflammasome signals were enhanced, but signals of IL-18 and adiponectin were decreased, in EAT of the coronary atherosclerotic lesions. We conclude that atherogenesis in human coronary arteries may be caused in part by NLR signals in infiltrating macrophage of epicardial adipose tissue.