Wang Yan, Xiong Lilin, Huang Xiaoquan, Ma Ying, Zou Lingyue, Liang Ying, Xie Wenjing, Wu Yongya, Chang Xiaoru, Wang Zhihui, Tang Meng
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China.
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, Jiangsu 210009, China; Department of Environmental Health, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, Jiangsu 210003, China.
J Hazard Mater. 2022 Feb 15;424(Pt A):127169. doi: 10.1016/j.jhazmat.2021.127169. Epub 2021 Sep 9.
Airborne particulate matter (PM) has been linked to cardiovascular diseases, but the underlying mechanisms remain unclear, especially at realistic exposure levels. In this study, both male and female BALB/c mice were employed to assess vascular homeostasis following a standard urban particulate matter, PM SRM1648a, via oropharyngeal aspiration at three environmentally relevant concentrations. The tested indicators included histopathological observation and lipid deposition, as well as redox biology and inflammatory responses. Furthermore, endothelial monolayer, vascular cell apoptosis and subcellular function were assessed to decipher whether episodic PM SRM1648a exposure leads to vascular damage after multiple periods of treatment, including subacute (4 weeks) and subchronic (8 weeks) durations. As a result, PM aspiration caused thickening of airways, leukocytes infiltration and adhesion to alveoli, with the spot of particles engulfed by pulmonary macrophages. Meanwhile, it induced local and systemic oxidative stress and inflammation, but limited pathological changes were captured throughout aortic tissues after either subacute or subchronic treatment. Furthermore, even in the absence of aortic impairment, vascular cell equilibrium has been disturbed by the characteristics of endothelial monolayer disintegration and cell apoptosis. Mechanistically, PM SRM1648a activated molecular markers of ER stress (BIP) and mitochondrial dynamics (DRP1) at both transcriptional and translational levels, which were strongly correlated to ox-inflammation and could serve as early checkpoints of hazardous events. In summary, our data basically indicate that episodic exposure of BALB/c mice to PM SRM1648a exerts limited effects on vascular histopathological alterations, but induces vascular cell apoptosis and subcellular dysfunction, to which local and systemic redox biology and inflammation are probably correlated.
空气中的颗粒物（PM）与心血管疾病有关，但其潜在机制仍不清楚，尤其是在实际暴露水平下。在本研究中，使用雄性和雌性BALB/c小鼠，通过口咽吸入三种与环境相关浓度的标准城市颗粒物PM SRM1648a，来评估血管稳态。测试指标包括组织病理学观察和脂质沉积，以及氧化还原生物学和炎症反应。此外，评估内皮单层、血管细胞凋亡和亚细胞功能，以解读在包括亚急性（4周）和亚慢性（8周）疗程的多个疗程后，间歇性暴露于PM SRM1648a是否会导致血管损伤。结果显示，吸入PM导致气道增厚、白细胞浸润并黏附于肺泡，肺部巨噬细胞吞噬了颗粒斑。同时，它诱导了局部和全身的氧化应激和炎症，但在亚急性或亚慢性治疗后，整个主动脉组织中观察到的病理变化有限。此外，即使在没有主动脉损伤的情况下，内皮单层解体和细胞凋亡的特征也扰乱了血管细胞平衡。从机制上讲，PM SRM1648a在转录和翻译水平上激活了内质网应激（BIP）和线粒体动力学（DRP1）的分子标记，它们与氧化炎症密切相关，可作为危险事件的早期检查点。总之，我们的数据基本表明，BALB/c小鼠间歇性暴露于PM SRM1648a对血管组织病理学改变影响有限，但会诱导血管细胞凋亡和亚细胞功能障碍，这可能与局部和全身的氧化还原生物学及炎症相关。
