Abstract

Exposure to fine particulate matter (PM_2.5) is closely linked with cardiovascular diseases. However, the underlying mechanism of PM_2.5 on cardiac function remains unknown. This study was aimed to investigate the role of microRNA-205 (miR-205) on PM_2.5-induced myocardial inflammation and cardiac dysfunction. PM_2.5 increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), following by decreased cell viability and antioxidant enzymes, resulting in apoptosis of cardiomyocytes (AC16). The histopathological and ultrastructural analysis demonstrated that PM_2.5 caused myocardial damage via interstitial edema, inflammatory cell infiltration, and myocardial fiber destruction. PM_2.5 enhanced the release of inflammatory factors in AC16 cells and heart tissue. Microarray analysis and dual-luciferase reporter gene assays demonstrated that PM_2.5-induced down-regulation of miR-205 regulated interleukin 1 receptor-associated kinase 2 (IRAK2), which further activated the TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-κB (NF-κB) signaling pathway in vivo. Moreover, the chemical mimics of miR-205 markedly inhibited the IRAK2/TRAF6/NF-κB signaling pathway, whereas the chemical inhibitors of miR-205 amplified PM_2.5-induced activation of the IRAK2 signaling pathway in vitro. In summary, our results found that PM_2.5 could trigger myocardial toxicity via miR-205 negative regulating the IRAK2/TRAF6/NF-κB signaling pathway. Our study suggests that miR-205 could be a promising target molecule for mitigating the hazardous effects of PM_2.5 on the cardiovascular system.

摘要

接触细颗粒物（PM _2.5）与心血管疾病密切相关。然而，PM _2.5对心脏功能的潜在机制仍然未知。这项研究旨在调查microRNA-205（miR-205）在PM _2.5诱导的心肌炎症和心脏功能障碍中的作用。PM _2.5增加了细胞的活力和抗氧化酶，从而增加了活性氧（ROS）和丙二醛（MDA）的水平，导致心肌细胞（AC16）凋亡。组织病理学和超微结构分析表明，PM _2.5通过间质性水肿，炎性细胞浸润和心肌纤维破坏引起心肌损害。下午_2.5增强了AC16细胞和心脏组织中炎性因子的释放。芯片分析和双荧光素酶报告基因分析表明，PM _2.5诱导的miR-205调节的白介素1受体相关激酶2（IRAK2）的下调，进一步激活了TNF受体相关因子6（TRAF6）/核转录因子-κB（NF-κB）体内信号传导途径。此外，的miR-205的模拟物的化学显着抑制IRAK2 / TRAF6 / NF-κB信号传导途径，而miR-205的化学抑制剂扩增PM _2.5的IRAK2信号传导途径的活化诱导的体外。总而言之，我们的结果发现PM _2.5可能通过miR-205负调控IRAK2 / TRAF6 /NF-κB信号通路触发心肌毒性。我们的研究表明，miR-205可能是缓解PM _2.5对心血管系统有害影响的有希望的靶分子。