Abstract
IntroductionInterleukin-1beta (IL-1β) is crucially involved in the pathogenesis of coronary atherosclerotic diseases (CAD) and its inhibition has proven cardiovascular benefits. Epicardial adipose tissue (EAT) is a local source of inflammatory mediators which may negatively affect the surrounding coronary arteries. In the present study, we explored the relationship between serum and EAT levels of IL-1β and IL-1 receptor antagonist (IL-1ra) in patients with chronic coronary syndrome (CCS) and recent acute coronary syndrome (ACS).MethodsWe obtained EAT biopsies in 54 CCS (Group 1) and 33 ACS (Group 2) patients undergoing coronary artery bypass grafting. Serum and EAT levels of IL-1β and IL-1ra were measured in all patients. An immunophenotypic study was carried out on EAT biopsies and the CD86 events were studied as markers of M1 macrophages.ResultsCirculating levels of IL-1β were significantly higher in the overall CAD population compared to a control group [7.64 pg/ml (6.86; 8.57) vs. 1.89 pg/ml (1.81; 2.29); p < 0.001]. In contrast, no differences were observed for serum IL-1ra levels between CAD and controls. Comparable levels of serum IL-1β were found between Groups 1 and 2 [7.6 pg/ml (6.9; 8.7) vs. 7.9 pg/ml (7.2; 8.6); p = 0.618]. In contrast, significantly lower levels of serum IL-1ra were found in Group 2 compared to Group 1 [274 pg/ml (220; 577) vs. 603 pg/ml (334; 1022); p = 0.035]. No differences of EAT levels of IL-1β were found between Group 2 and Group 1 [3.4 pg/ml (2.3; 8.4) vs. 2.4 pg/ml (1.9; 8.0); p = 0.176]. In contrast, significantly lower EAT levels of IL-1ra were found in Group 2 compared to Group 1 [101 pg/ml (40; 577) vs. 1344 pg/ml (155; 5327); p = 0.002]. No correlation was found between EAT levels of IL-1β and CD86 and CD64 events.ConclusionThe present study explores the levels of IL-1β and IL-1ra in the serum and in EAT of CCS and ACS patients. ACS seems to be associated to a loss of the counter-regulatory activity of IL-1ra against the pro-inflammatory effects related to IL-1β activation.
Highlights
Interleukin-1beta (IL-1β) is crucially involved in the pathogenesis of coronary atherosclerotic diseases (CAD) and its inhibition has proven cardiovascular benefits
The aim of the present study is to investigate the behavior of IL-1β and IL-1 receptor antagonist (IL-1ra), at serum and Epicardial adipose tissue (EAT) levels, in patients referred to elective coronary artery bypass grafting (CABG) for a chronic coronary syndrome (CCS) resistant to optimized medical therapy, and in patients referred to urgent CABG after a recent non-ST-segment elevation acute coronary syndrome (ACS) syndrome
The main findings of the present study were: (1) CAD patients showed higher EAT thickness and circulating levels of IL1β compared to controls; (2) despite similar circulating levels of IL-1β, ACS patients showed lower serum and EAT levels of IL-1ra compared to CCS patients; (3) serum and EAT levels of IL1-ra were directly correlated; (4) there was no correlation between IL-1β and IL-1ra levels either at local or at systemic levels
Summary
Interleukin-1beta (IL-1β) is crucially involved in the pathogenesis of coronary atherosclerotic diseases (CAD) and its inhibition has proven cardiovascular benefits. Interleukin-1beta (IL-1β) is a proinflammatory cytokine and its role in promoting inflammation in coronary atherosclerotic diseases (CAD) has been widely explored (Dinarello, 2011). It plays an important role in the inflammatory cascade and coordinates the cellular response to tissue injury promoting the recruitment of inflammatory cells and the increased production of other cytokines (Dinarello, 2011). This study has demonstrated that targeting the IL-1β innate immunity pathway with canakinumab significantly reduces the recurrence of new cardiovascular events (Ridker et al, 2017)
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