Tacrolimus reduces atherosclerotic plaque formation in ApoE(−/−) mice by inhibiting NLRP3 inflammatory corpuscles

Effect of tacrolimus on atherosclerotic plaques and its influence on Nod-like receptor protein 3 (NLRP3) inflammatory pathway were studied by establishing the mouse model of atherosclerosis. The mice were divided into 3 groups: C57BL/6 mouse group (WT group), ApoE(−/−) mouse group (ApoE(−/−) group) and ApoE(−/−) mouse + tacrolimus intervention group (ApoE(−/−) + Tac group). The area of atherosclerotic plaques and the pathological morphologic changes were observed. The NLRP3, interleukin-1β (IL-1β), IL-18, NLRP3 inflammatory corpuscles, pro-inflammatory factors IL-1β and IL-18 in the aorta were analyzed. The area of atherosclerotic plaques in ApoE(−/−) mice was increased significantly, and it was significantly reduced after tacrolimus intervention. After tacrolimus intervention, the arterial intima became obviously thinner and no obvious cholesterol crystals were observed. The macrophage infiltration in atherosclerotic plaques was significantly increased, and the content of smooth muscle cells was also increased. The levels of serum IL-1β, IL-18 and NLRP3 in ApoE(−/−) mice were significantly increased, and they remarkably declined after tacrolimus intervention. ROS content in atherosclerotic plaques was increased in ApoE(−/−) mice, and it remarkably declined after tacrolimus intervention. The protein content of NLRP3, ASC, Casp-1, IL-1β and IL-18 in the aorta in ApoE(−/−) mice was remarkably increased, and they were inhibited to some extent after tacrolimus intervention. In conclusion, it is speculated that tacrolimus may reduce the formation of AS through inhibiting ROS in macrophages and activation of NLRP3 inflammatory corpuscles and reducing the release of IL-1β and IL-18.