期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 182, 期 -, 页码 171-181出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.02.027
关键词
Silica nanoparticles; Pyroptosis; Cardiac hypertrophy; Inflammation; ROS; NLRP3; Caspase-1 pathway
资金
- National Natural Science Foundation of China [81930091, 81773462, 81973077]
Exposure to SiNPs may lead to cardiac hypertrophy and pyroptosis, possibly through the ROS/NLRP3/Caspase-1 signaling pathway.
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.
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