Silence of NLRP3 Suppresses Atherosclerosis and Stabilizes Plaques in Apolipoprotein E-Deficient Mice

OBJECTIVES The role of the NLRP3 inflammasome in atherosclerosis remains controversial. The aim of this study was to determine whether inhibition of NLRP3 signaling by lentivirus-mediated RNA interference could reduce atherosclerosis and stabilizes plaques. We also tried to explore the mechanisms of the impact of NLRP3 inflammasome on atherosclerosis. METHODS Apolipoprotein E-deficient mice aged 8 weeks were fed a high-fat diet and were injected with NLRP3 interfering or mock viral suspension after 4 weeks. Lentivirus transfer was repeated in 2 weeks. Four weeks after the first lentivirus injection, we evaluated the effects of NLRP3 gene silencing on plaque composition and stability and on cholesterol efflux and collagen metabolism, by histopathologic analyses and real-time PCR. RESULTS Gene silence of NLRP3 prevented plaques progression and inhibited inductions of proinflammatory cytokines. Moreover, this RNA interference reduced plaque content of macrophages and lipid, and increased plaque content of smooth muscle cells and collagen, leading to the stabilizing of atherosclerotic plaques. CONCLUSIONS NLRP3 inflammasomes may play a vital role in atherosclerosis, and lentivirus-mediated NLRP3 silencing would be a new strategy to inhibit plaques progression and to reduce local inflammation.