The involvement of DRP1-mediated caspase-1 activation in inflammatory response by urban particulate matter in EA.hy926 human vascular endothelial cells. (15th October 2021)

• Record Type: Journal Article
• Authors: Wang, Yan; Xiong, Lilin; Yao, Yongshuai; Ma, Ying; Liu, Qing; Pang, Yanting; Tang, Meng
• Is Part Of: Environmental pollution. Volume 287(2021)
• Publication Date: 2021-10-15
• Subjects: Particulate matter -- Mitochondrial dynamics -- Mitochondrial fission -- Inflammatory response -- Pyroptosis; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.117369
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: DRP1 is responsible for PM SRM1648a-induced mitochondrial fission in EA.hy926 endothelial cells. PM SRM1648a triggers caspase-1 activation and IL-1β release in human vascular endothelial cells. DRP1/caspase-1/IL-1β axis is involved in inflammatory response in EA.hy926 cells following PM SRM1648a. Caspase-1-dependent pyroptosis is not the main form of cell death in PM SRM1648a-treated EA.hy926 cells. Abstract : DRP1/caspase-1/IL-1β signaling pathway is responsible for inflammatory response in EA.hy926 cells by PM SRM1648a.