Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China; Sinopharm North Hospital, Baotou, 014040, PR China.
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China.
Free Radic Biol Med. 2022 Mar;182:171-181. doi: 10.1016/j.freeradbiomed.2022.02.027. Epub 2022 Feb 24.
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-1β) in heart tissue. In addition, SiNPs could upregulate the expressions of cardiac hypertrophy-related special marker including ANP, BNP, β-MHC, it also elevated the pyroptosis-related protein, such as NLRP3, Cleaved-Caspase-1, GSDMD, IL-18 and Cleaved-IL-1β 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-1β, ANP, BNP and β-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.
越来越多的文献表明，二氧化硅纳米颗粒（SiNPs）暴露与不良心血管效应有关。心肌肥厚是心力衰竭最常见的危险因素之一。然而，SiNPs 是否参与心肌肥厚以及潜在的机制仍未被探索。本研究旨在探讨 SiNPs 对细胞焦亡和心肌肥厚的分子机制。体内结果发现，SiNPs 诱导了心脏组织的超微结构改变和组织病理学损伤，伴随着氧化损伤的发生和炎症因子（IL-18 和 IL-1β）水平的升高。此外，SiNPs 可以上调心肌肥厚相关的特殊标志物的表达，包括 ANP、BNP、β-MHC，也上调了细胞焦亡相关蛋白，如 NLRP3、Cleaved-Caspase-1、GSDMD、IL-18 和 Cleaved-IL-1β。在体外研究中，SiNPs 增加了心肌细胞内 ROS 的产生，并激活了 NLRP3/Caspase-1/GSDMD 信号通路。而 NADPH 氧化酶（NOX）抑制剂 VAS2870 有效抑制了 ROS 水平，并抑制了 NLRP3、ASC、Pro-Caspase-1、Cleaved-Caspase-1、N-GSDMD、IL-18、Cleaved-IL-1β、ANP、BNP 和 β-MHC 的表达。此外，在心肌细胞中转染 si-NLRP3 或采用 Caspase-1 抑制剂 VX-765，对 SiNPs 诱导的细胞焦亡和心肌肥厚具有抑制作用。综上所述，我们的研究结果表明，SiNPs 通过 ROS/NLRP3/Caspase-1 信号通路引发细胞焦亡和心肌肥厚。
