大气细颗粒物PM2.5是雾霾天气形成的首要污染物。流行病学研究表明，PM2.5暴露能显著增加呼吸系统和心血管疾病的发病率和死亡率。PM2.5易富集有毒物质进入体内，引起心肌细胞凋亡和心脏功能紊乱，但目前PM2.5引起心肌损伤和心功能紊乱的分子机制尚不完全明确。申请人前期发现，短期PM2.5暴露引发的心肌损伤和心功能失常与肺损伤后释放的细胞外囊泡(EV)有关，EV介导的肺-心间cross-talk触发了PM2.5的心肌毒性。在前期研究基础上，本项目将围绕PM2.5诱发心肌损伤的病理学效应，通过无创气管内滴注、肺及细支气管离体培养、体外细胞对话三个维度，侧重EV-miR421-ACE2介导的肺-心间对话，深入研究PM2.5暴露引发心肌损伤的分子机制，不仅能加深对肺-心cross-talk的理解，还可丰富PM2.5毒理学的基础理论，为环境相关心血管疾病的临床干预提供新思路。

Atmospheric fine particulate matter PM2.5 (aerodynamic diameter ≤ 2.5μm) is the primary pollutant contributing to the haze weather. Accumulating epidemiological studies show that exposure to PM2.5 significantly increases the morbidity and mortality of respiratory and cardiovascular diseases. Owing to its small size, PM2.5 is prone to accumulate toxic substances and enter the body, causing cardiomyocyte apoptosis. However, the molecular mechanism of PM2.5-induced myocardial injury and cardiac dysfunction remains unknown. Our preliminary results demonstrated that short-term exposure to PM2.5 could further induce cardiac dysfunction after lung injury, which is associated with extracellular vesicles-mediated ‘pulmonary to heart ’cross-talk. The present investigation is based on our previous research and focus on PM2.5 exposure induced lung injury contributing to myocardial injury. Intratracheal instillation in mice, ex-vivo culture of lung and bronchiole, and cross-talk study in vitro was respectively used to investigate the cross-talk between lung and heart. We focus on the mechanism of EV-miR421-ACE2 axis in PM2.5-induced myocardial injury, and aim to reveal the mechanism of PM2.5 toxicity. EV-miR421-ACE2 might be a novel therapeutic target for PM2.5-induced cardiovascular diseases, which could enrich the knowledge of molecular pathology for environmental health issues.