Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, Jiangsu, 210009, China.
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, Jiangsu, 210009, China; Department of Environmental Health, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, Jiangsu, 210003, China.
Environ Pollut. 2021 Oct 15;287:117369. doi: 10.1016/j.envpol.2021.117369. Epub 2021 May 24.
Atmospheric particulate matter (PM) has been reported to be closely related to cardiovascular adverse events. However, the underlying mode of action remains to be elucidated. Previous studies have documented that PM induces mitochondrial damage and inflammation, the relation between these two biological outcomes is still unclear though. In this study, we used EA.hy926 human vascular endothelial cells and a standard PM, PM SRM1648a to study the potential effects of mitochondrial dysfunction on endothelial inflammatory responses. As a result, PM SRM1648a changes mitochondrial morphology and interrupts mitochondrial dynamics with a persistent tendency of fission in a dose-dependent manner. Additionally, the caspase-1/IL-1β axis is involved in inflammatory responses but not cell pyroptosis in EA.hy926 cells following the exposure to PM SRM1648a. The activation of caspase-1 has implications in inflammation but not pyroptosis, because caspase-1-dependent pyroptosis is not the main modality of cell death in PM SRM1648a-treated EA.hy926 cells. With regard to the association between mitochondrial damage and inflammation in the case of particle stimulation, DRP1-mediated mitochondrial fission is responsible for inflammatory responses as a result of caspase-1 activation. The current study showed that PM SRM1648a has the ability to disturb mitochondrial dynamics, and trigger endothelial inflammation via DRP1/caspase-1/IL-1β regulatory pathway. In a conclusion, mitochondrial fission enables EA.hy926 cells to facilitate caspase-1 activation in response to PM SRM1648a, which is a crucial step for inflammatory reaction in vascular endothelial cells.
大气颗粒物 (PM) 与心血管不良事件密切相关。然而，其作用机制仍有待阐明。先前的研究表明，PM 可诱导线粒体损伤和炎症，尽管这两种生物效应之间的关系尚不清楚。在这项研究中，我们使用 EA.hy926 人血管内皮细胞和标准 PM（PM SRM1648a）来研究线粒体功能障碍对内皮炎症反应的潜在影响。结果表明，PM SRM1648a 以剂量依赖的方式改变线粒体形态并中断线粒体动力学，具有持续的分裂趋势。此外，caspase-1/IL-1β 轴参与炎症反应，但不参与 EA.hy926 细胞暴露于 PM SRM1648a 后的细胞焦亡。caspase-1 的激活与炎症有关，但与细胞焦亡无关，因为 caspase-1 依赖性焦亡不是 PM SRM1648a 处理的 EA.hy926 细胞的主要死亡方式。关于颗粒刺激情况下线粒体损伤和炎症之间的关系，DRP1 介导的线粒体分裂导致 caspase-1 激活，从而引发炎症反应。本研究表明，PM SRM1648a 能够通过 DRP1/caspase-1/IL-1β 调节途径干扰线粒体动力学，并引发内皮炎症。总之，线粒体分裂使 EA.hy926 细胞能够在 PM SRM1648a 作用下激活 caspase-1，这是血管内皮细胞炎症反应的关键步骤。
