Activation of NALP3/inflammasome pathway in circulating monocytes and epicardial adipose tissue of patients with acute coronary syndromes

Abstract

Purpose: Interleukin-1β (IL-1β) is a potent inflammatory cytokine. Processing of active IL-1β depends on activation of a protein complex termed inflammasome. Several inflammasomes have been described with NALP3 representing the most intensely studied. We sought to evaluate NALP3 and IL-1β expression by circulating monocytes and epicardial adipose tissue (EAT) of patients with Non-ST elevation acute coronary syndromes (ACS), chronic stable angina (SA) and controls (C). Methods: EAT samples were obtained during coronary artery bypass grafting from ACS (n=10) and SA (n=10) patients, and as controls, from patients with angiographically normal coronary arteries undergoing surgery for mitral insufficiency (C; n=10). Circulating monocytes were isolated by magnetic beads from peripheral blood and stimulated for 4-24h with LPS (10 ng/ml). NALP3 and proIL-1β mRNA expressions were evaluated with a Sybr Green qRT-PCR. Results: At baseline, ACS had higher NALP3 and proIL-1β expression in circulating monocytes as compared with SA and C (P<0.05 for all comparisons). In all groups, a significant increase of NALP3 and proIL-1β expression was observed after 4h of LPS-challenge (P<0.05 baseline vs 4h for all comparisons). In ACS, NALP3 and proIL-1β expressions were still elevated after 24h of LPS-challenge, while in SA and C they returned to baseline (Fig. 1A). Moreover, ACS had higher NALP3 expression in EAT (Fig. 1B). ![Figure][1] Conclusions: Circulating monocytes of ACS had a constitutive higher and a sustained expression of NALP3 and proIL-1β. Moreover, for the first time, we demonstrated that ACS is associated with NALP3/inflammasome pathway activation directly into EAT surrounding diseased coronary arteries. These findings add new elements to the pathogenesis of ACS and suggest novel therapeutic targets. [1]: pending:yes