Related Experiment Video
Updated: Apr 27, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Silence of NLRP3 suppresses atherosclerosis and stabilizes plaques in apolipoprotein E-deficient mice
Fei Zheng1, Shanshan Xing2, Zushun Gong1
1Department of Cardiology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China.
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.
Insights
NLRP3 inflammasome inhibition via lentivirus-mediated RNA interference prevented atherosclerosis progression. This approach stabilized plaques by reducing inflammation and lipid content, offering a novel therapeutic strategy.
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- The role of the NLRP3 inflammasome in atherosclerosis is debated.
- Atherosclerotic plaques are characterized by inflammation, lipid accumulation, and plaque instability.
Purpose of the Study:
- To investigate if inhibiting NLRP3 inflammasome signaling using lentivirus-mediated RNA interference can reduce atherosclerosis.
- To determine if NLRP3 inhibition stabilizes atherosclerotic plaques.
- To explore the underlying mechanisms of NLRP3 inflammasome's impact on atherosclerosis.
Main Methods:
- Apolipoprotein E-deficient mice on a high-fat diet were used.
- Lentivirus-mediated RNA interference targeting NLRP3 was administered.
- Histopathological analyses and real-time PCR were employed to assess plaque composition, stability, cholesterol efflux, and collagen metabolism.
Main Results:
- NLRP3 gene silencing inhibited plaque progression and pro-inflammatory cytokine induction.
- RNA interference reduced macrophage and lipid content within plaques.
- Plaque smooth muscle cell and collagen content increased, leading to plaque stabilization.
Conclusions:
- NLRP3 inflammasomes are crucial in the pathogenesis of atherosclerosis.
- Lentivirus-mediated NLRP3 silencing presents a potential therapeutic strategy for inhibiting plaque progression and reducing inflammation in atherosclerosis.
Related Concept Videos
01:26Atherosclerosis III: Management
01:38Inflammation
01:30Atherosclerosis I: Introduction
02:15Experimental RNAi