Despite the air quality has been generally improved in recent years, ambient fine particulate matter (PM2.5), a major contributor to air pollution, remains one of the major threats to public health. Vascular calcification is a systematic pathology associated with an increased risk of cardiovascular disease. Although the epidemiological evidence has uncovered the association between PM2.5 exposure and vascular calcification, little is known about the underlying mechanisms. The adverse outcome pathway (AOP) concept offers a comprehensive interpretation of all of the findings obtained by toxicological and epidemiological studies. In this review, reactive oxygen species (ROS) generation was identified as the molecular initiating event (MIE), which targeted subsequent key events (KE) such as oxidative stress, inflammation, endoplasmic reticulum (ER) stress, and autophagy, from the cellular to the tissue/organ level. These KEs eventually led to the adverse outcome (AO), namely increased incidence of vascular calcification and atherosclerosis morbidity. To the best of our knowledge, this is the first AOP framework devoted to PM2.5-associated vascular calcification, which benefits future investigations by identifying current limitations and latent biomarkers.

中文翻译：

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对空气污染相关心血管疾病的新见解：PM2.5相关血管钙化的不良结果途径框架

尽管近年来空气质量普遍改善，但空气污染的主要来源之一环境细颗粒物（PM2.5）仍然是公众健康的主要威胁之一。血管钙化是一种与心血管疾病风险增加相关的系统病理学。尽管流行病学证据已揭示 PM2.5 暴露与血管钙化之间的关联，但对其潜在机制知之甚少。不良结果途径（AOP）概念对毒理学和流行病学研究获得的所有结果提供了全面的解释。在这篇综述中，活性氧（ROS）的产生被确定为分子起始事件（MIE），它针对随后的关键事件（KE），如氧化应激、炎症、内质网（ER）应激和自噬，从细胞到组织/器官水平。这些 KE 最终导致不良后果 (AO)，即血管钙化和动脉粥样硬化发病率增加。据我们所知，这是第一个致力于 PM2.5 相关血管钙化的 AOP 框架，通过识别当前的局限性和潜在的生物标志物，有利于未来的研究。