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PM2 .5 induces endothelial dysfunction via activating NLRP3 inflammasome
Author(s) -
Hu Tingting,
Zhu Ping,
Liu Yihai,
Zhu Haoran,
Geng Jin,
Wang Bingjian,
Yuan Guoliang,
Peng Yuzhu,
Xu Biao
Publication year - 2021
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.23309
Subject(s) - inflammasome , downregulation and upregulation , enos , proinflammatory cytokine , reactive oxygen species , umbilical vein , chemistry , endothelial dysfunction , endothelial stem cell , viability assay , gene knockdown , microbiology and biotechnology , immunology , cell , in vitro , biology , inflammation , nitric oxide , biochemistry , apoptosis , receptor , endocrinology , nitric oxide synthase , gene , organic chemistry
PM2.5 (particulate matter <2.5 μm in diameter) is proven to contribute to the development of atherosclerosis. Endothelial cell dysfunction is the initial step of atherosclerosis. The underlying mechanisms of endothelial cell damage exposed to PM2.5 are still obscure. In our study, PM2.5 was administrated to C57BL/6 male mice by intranasal instillation for 2 weeks. Human umbilical vein endothelial cells (HUVECs) were also treated with PM2.5 to evaluate the adverse effect in vitro. The immunohistochemical staining of aortas showed that the expressions of proinflammatory cytokines and endothelial adhesion markers were significantly increased in PM2.5‐exposed mice than that in saline‐exposed mice. In vitro, PM2.5 could inhibit HUVECs viability and impair cell migration in a concentration‐dependent manner. Besides, PM2.5 exposure downregulated eNOS expression while upregulated reactive oxygen species (ROS) levels. Mechanistically, PM2.5 activated the NLRP3 inflammasome in HUVECs while knockdown of NLRP3 could effectively reverse the downregulation of eNOS expression and production of ROS after PM2.5 exposure. In summary, our data showed that PM2.5 could cause endothelial dysfunction, and probably via NLRP3 inflammasome activation.