Acute and chronic exposure to particulate matter (PM) 2.5 is associated with adverse health effect upon the cardiovascular (CV) system. However, the molecular mechanism by which PM2.5 evokes CV injuries has not been fully clarified. In our recent report, we demonstrate that exposure to PM2.5 leads to elevation of circulating angiotensin II (ANGII) levels and local expressions of angiotensinogen (AGT, the precursor of ANGII), angiotensin-converting enzyme (ACE) and ANGII type 1 receptor (AT1R) in the vascular endothelial cells, which subsequently instigates the oxidative stress and proinflammatory response in the vascular endothelium. In the present study, we disclosed that PM2.5 exposure induced the activation of the transcriptional factor AP-1 and its components, c-Jun and ATF2, in the human vascular endothelial cells. Although the DNA-binding sites for AP-1 were identified within the promoter regions of AGT, ACE and AT1R genes, RT-PCR and immunoblot assays indicated that AP-1 transactivation was only involved in AT1R upregulation, but did not affect the induction of AGT and ACE expression under the same conditions. Furthermore, ERKs and p38K functioned as the upstream protein kinases involving in AP-1 transactivation and AT1R upregulation under PM2.5 stimulation. In addition, the oxidative stress and proinflammatory responses in the PM2.5-treated vascular endothelial cells were significantly reduced when MAPKs and AP-1 activation were inhibited. Therefore, we conclude that PM2.5 exposure induces MAPK/AP-1 cascade activation, which contributes to AT1R upregulation and vascular endothelial dysfunction. Identifying novel therapeutic targets to alleviate AP-1 transactivation and restore AT1R expression may be helpful for the management of PM2.5-induced CV burden.

急性和慢性暴露于颗粒物（PM）2.5与对心血管（CV）系统的不良健康影响相关。但是，尚未完全阐明PM2.5引起CV损伤的分子机制。在我们的最新报告中，我们证明了暴露于PM2.5会导致循环中的血管紧张素II（ANGII）水平升高以及血管紧张素原（AGT，ANGII的前体），血管紧张素转化酶（ACE）和ANGII 1型受体的局部表达（AT1R）在血管内皮细胞中的表达，从而促进了血管内皮中的氧化应激和促炎反应。在本研究中，我们披露了PM2.5暴露可诱导人血管内皮细胞中转录因子AP-1及其组分c-Jun和ATF2的活化。AGT，ACE和AT1R基因，RT-PCR和免疫印迹分析表明，AP-1反式激活仅参与AT1R的上调，但在相同条件下不影响AGT和ACE表达的诱导。此外，ERK和p38K充当上游蛋白激酶，在AP2.5刺激下参与AP-1反式激活和AT1R上调。此外，当MAPKs和AP-1激活被抑制时，经PM2.5处理的血管内皮细胞的氧化应激和促炎反应显着降低。因此，我们得出结论，PM2.5暴露会诱导MAPK / AP-1级联激活，从而导致AT1R上调和血管内皮功能障碍。确定减轻AP-1反式激活和恢复AT1R表达的新治疗靶点可能有助于PM2.5诱导的CV负担的管理。