Aernoud Fiolet

280 Chapter 11 signaling. However, released inflammasome particles, and inflammasome derived exosomes have been described to have the ability to act as danger signals to increase inflammation in surrounding macrophages. 16,39,40 NLRP3 in coronary disease and the effects of colchicine on inflammatory markers The finding that EV NLRP3 protein levels are reduced in patients with chronic coronary disease that were treated with colchicine indicates that inhibitory effects on the NLRP3 inflammasome might contribute to the atheroprotective effects of colchicine in coronary disease. Additional analyses of the CANTOS trial population revealed a residual risk for cardiovascular events that is associated with higher levels of IL-18 and IL-6. 41 . NLRP3 inflammasome inhibition may lead to the attenuation of both IL-1 β and IL-18 levels. 42 This contributes to the hypothesis that NLRP3 inflammasome inhibition, compared to selective targeting of IL-1 β with canakinumab, has the potential to more effectively reduce cardiovascular events in patients with established coronary disease. However, this remains to be proven. 41 Data on direct measurements of NLRP3 inflammasome components such as NLRP3 protein in relation to atherosclerosis and coronary disease are limited. NLRP3 expression and downstream cytokines were increased in peripheral blood mononuclear cells and monocytes of patients with coronary disease compared to healthy controls. 43,44 Furthermore, lower levels of NLRP3 are associated with less severe angiographically assessed coronary disease. 44 Higher hs-CRP and IL-6 levels are associated with an increased risk for cardiovascular events. 45,46 The CANTOS included patients with a history of myocardial infarction and a baseline level of hs-CRPabove 2mg/L. 3 Cardiovascular benefits of canakinumabwere largest among thosewho achieved lowest levels of hs- CRP and IL-6. 47,48 We previously showed a reduction in hs-CRP and IL-6 following 30 days of colchicine treatment in patients with chronic coronary disease and hs- CRP above 2 mg/L. 49 In the current study, with no hs-CRP criteria on inclusion, we also observed a reduction in hs-CRP. We were not able to investigate the relation between colchicine induced hs-CRP reduction and the risk of cardiovascular events. Here, we demonstrate that colchicine reduces EVNLRP3 protein levels in patients with chronic coronary disease. The NLRP3 inflammasome is a pivotal driver of