Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/ NLRP3/Caspase-1 pathway

被引:94
作者
Wang, Fenghong [1 ,2 ,3 ]
Liang, Qingqing [1 ,2 ]
Ma, Yuexiao [1 ,2 ]
Sun, Mengqi [1 ,2 ]
Li, Tianyu [1 ,2 ]
Lin, Lisen [1 ,2 ]
Sun, Zhiwei [1 ,2 ]
Duan, Junchao [1 ,2 ]
机构
[1] Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing 100069, Peoples R China
[2] Capital Med Univ, Beijing Key Lab Environm Toxicol, Beijing 100069, Peoples R China
[3] Sinopharm North Hosp, Baotou 014040, Peoples R China
基金
中国国家自然科学基金;
关键词
Silica nanoparticles; Pyroptosis; Cardiac hypertrophy; Inflammation; ROS; NLRP3; Caspase-1; pathway; ISCHEMIA-REPERFUSION INJURY; NLRP3; INFLAMMASOME; IL-1-BETA; DEATH;
D O I
10.1016/j.freeradbiomed.2022.02.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Growing literatures suggest that silica nanoparticles (SiNPs) exposure is correlated with adverse cardiovascular effects. Cardiac hypertrophy is one of the most common risk factors for heart failure. However, whether SiNPs involved in cardiac hypertrophy and the underlying mechanisms was remained unexploited. Our study aimed to investigate the molecular mechanisms of SiNPs on pyroptosis and cardiac hypertrophy. The in vivo results found that SiNPs induced ultrastructural change and histopathological damage, accompanied by oxidative damage occurred and increased levels of inflammatory factors (IL-18 and IL-1 beta) in heart tissue. In addition, SiNPs could upregulate the expressions of cardiac hypertrophy-related special marker including ANP, BNP, beta-MHC, it also elevated the pyroptosis-related protein, such as NLRP3, Cleaved-Caspase-1, GSDMD, IL-18 and Cleaved-IL-1 beta in vivo. For in vitro study, SiNPs increased the intracellular ROS generation and activated the NLRP3/Caspase-1/ GSDMD signaling pathway in cardiomyocytes. Whereas, the NADPH oxidase (NOX) inhibitor VAS2870 had effectively inhibited the ROS level and suppressed the expression of NLRP3, ASC, Pro-Caspase-1, Cleaved-Caspase-1, N-GSDMD, IL-18, Cleaved-IL-1 beta, ANP, BNP and beta-MHC. Moreover, transfected with si-NLRP3 or adopted with Caspase-1 inhibitor VX-765 in cardiomyocytes showed an inhibitory effect on SiNPs-induced pyroptosis and cardiac hypertrophy. In summary, our results demonstrated that SiNPs could trigger pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 signaling pathway.
引用
收藏
页码:171 / 181
页数:11
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