Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
J Hazard Mater. 2022 May 15;430:128368. doi: 10.1016/j.jhazmat.2022.128368. Epub 2022 Jan 29.
Fine particulate matter (PM) exposure is a major threat to public health, and is listed as one of the leading factors associated with global premature mortality. Among the adverse health effects on multiple organs or tissues, the influence of PM exposure on cardiovascular system has drawn more and more attention. Although numerous studies have investigated the mechanisms responsible for the cardiovascular toxicity of PM, the various mechanisms have not been integrated due to the variety of the study models, different levels of toxicity assessment endpoints, etc. Adverse Outcome Pathway (AOP) framework is a useful tool to achieve this goal so as to facilitate comprehensive understanding of toxicity assessment of PM on cardiovascular system. This review aims to illustrate the causal mechanistic relationships of PM-triggered cardiovascular toxicity from different levels (from molecular/cellular/organ to individual/population) by using AOP framework. Based on the AOP Wiki and published literature, we propose an AOP framework focusing on the cardiovascular toxicity induced by PM exposure. The molecular initiating event (MIE) is identified as reactive oxygen species generation, followed by the key events (KEs) of oxidative damage and mitochondria dysfunction, which induces vascular endothelial dysfunction via vascular endothelial cell autophagy dysfunction, vascular fibrosis via vascular smooth muscle cell activation, cardiac dysregulation via myocardial apoptosis, and cardiac fibrosis via fibroblast proliferation and myofibroblast differentiation, respectively; all of the above cardiovascular injuries ultimately elevate cardiovascular morbidity and mortality in the general population. As far as we know, this is the first work on PM-related cardiovascular AOP construction. In the future, more work needs to be done to explore new markers in the safety assessment of cardiovascular toxicity induced by PM.
细颗粒物（PM）暴露是对公众健康的主要威胁，被列为与全球过早死亡相关的主要因素之一。在对多个器官或组织的不良健康影响中，PM 暴露对心血管系统的影响引起了越来越多的关注。尽管许多研究已经探讨了 PM 对心血管毒性的作用机制，但由于研究模型的多样性、毒性评估终点的不同水平等原因，各种机制尚未得到整合。不良结局途径（AOP）框架是实现这一目标的有用工具，有助于全面了解 PM 对心血管系统毒性的评估。本综述旨在通过 AOP 框架阐明 PM 引发心血管毒性的不同水平（从分子/细胞/器官到个体/人群）的因果机制关系。基于 AOP Wiki 和已发表的文献，我们提出了一个专注于 PM 暴露引起的心血管毒性的 AOP 框架。分子起始事件（MIE）被确定为活性氧的产生，随后是氧化损伤和线粒体功能障碍的关键事件（KEs），这些事件通过血管内皮细胞自噬功能障碍导致血管内皮功能障碍，通过血管平滑肌细胞激活导致血管纤维化，通过心肌细胞凋亡导致心脏调节障碍，以及通过成纤维细胞增殖和肌成纤维细胞分化导致心脏纤维化；所有这些心血管损伤最终导致普通人群心血管发病率和死亡率的上升。据我们所知，这是关于 PM 相关心血管 AOP 构建的第一项工作。在未来，需要做更多的工作来探索 PM 诱导的心血管毒性安全评估中的新标志物。
