Fig. 1

Role of IL-33/ST2 axis on heart failure and coronary atherosclerosis. IL-33 binds to the heterodimeric complex of ST2L and IL-1 receptor accessory protein on the cell membrane, activating downstream signal transduction. In the context of heart failure, IL-33 has shown to attenuate the activation of the MAPK pathway and NF-κB, which are responsible for fibrosis and inflammation [3]. Additionally, IL-33 also reduces the expression of HMGB1 and inhibits the release of Th1 cytokines (IL-6, TNF-β, INF-γ), preventing cardiomyocytes from hypertrophy and apoptosis [4]. In coronary atherosclerosis, IL-33 increases Th2 cytokines and cholesterol efflux gene expression, resulting in reduction of foam cells [5, 6]. A fraction of the IL-33 released as an “alarmin” signal from necrotic cell is neutralized by soluble ST2 (“decoy” receptor), which inhibit cardiovascular protective effect of IL-33/ST2 axis. ST2L ST2 transmembrane ligand, IL-1RAcP Interleukin-1 receptor accessory protein, HMGB High-mobility group box 1, SMC smooth muscle cell, Mφ macrophage