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.

中文翻译：

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PM2.5通过激活NLRP3炎症小体诱导内皮功能障碍

PM2.5（直径小于 2.5 微米的颗粒物）被证明有助于动脉粥样硬化的发展。内皮细胞功能障碍是动脉粥样硬化的第一步。暴露于 PM2.5 的内皮细胞损伤的潜在机制仍不清楚。在我们的研究中，通过鼻内滴注对 C57BL/6 雄性小鼠施用 PM2.5 2 周。人脐静脉内皮细胞 (HUVEC) 也用 PM2.5 处理，以评估体外的不利影响。主动脉免疫组化染色显示，PM2.5暴露小鼠的促炎细胞因子和内皮粘附标志物的表达明显高于盐水暴露小鼠。在体外，PM2.5 可以以浓度依赖的方式抑制 HUVECs 的活力并损害细胞迁移。此外，PM2. 5 暴露下调 eNOS 表达，同时上调活性氧 (ROS) 水平。从机制上讲，PM2.5 激活 HUVEC 中的 NLRP3 炎症小体，而敲除 NLRP3 可以有效逆转 PM2.5 暴露后 eNOS 表达的下调和 ROS 的产生。总之，我们的数据显示 PM2.5 可能导致内皮功能障碍，并且可能通过 NLRP3 炎症小体激活。