Exposure to particulate air pollution is a major environmental risk factor for cardiovascular mortality and morbidity, on a global scale. Both acute and chronic cardiovascular impacts have so far been attributed to particulate-mediated oxidative stress in the lung and/or via ‘secondary’ pathways, including endothelial dysfunction, and inflammation. However, increasing evidence indicates the translocation of inhaled nanoparticles to major organs via the circulation. It is essential to identify the composition and intracellular targets of such particles, since these are likely to determine their toxicity and consequent health impacts. Of potential major concern is the abundant presence of iron-rich air pollution nanoparticles, emitted from a range of industry and traffic-related sources. Bioreactive iron can catalyse formation of damaging reactive oxygen species, leading to oxidative stress and cell damage or death.

Here, we identify for the first time, in situ, that exogenous nanoparticles (~15–40 nm diameter) within myocardial mitochondria of young, highly-exposed subjects are dominantly iron-rich, and co-associated with other reactive metals including aluminium and titanium. These rounded, electrodense nanoparticles (up to ~ 10 x more abundant than in lower-pollution controls) are located within abnormal myocardial mitochondria (e.g. deformed cristae; ruptured membranes). Measurements of an oxidative stress marker, PrP^C and an endoplasmic reticulum stress marker, GRP78, identify significant ventricular up-regulation in the highly-exposed vs lower-pollution controls. In shape/size/composition, the within-mitochondrial particles are indistinguishable from the iron-rich, combustion- and friction-derived nanoparticles prolific in roadside/urban environments, emitted from traffic/industrial sources. Incursion of myocardial mitochondria by inhaled iron-rich air pollution nanoparticles thus appears associated with mitochondrial dysfunction, and excess formation of reactive oxygen species through the iron-catalyzed Fenton reaction. Ventricular oxidative stress, as indicated by PrP^C and GRP78 up-regulation, is evident even in children/young adults with minimal risk factors and no co-morbidities. These new findings indicate that myocardial iron overload resulting from inhalation of airborne, metal-rich nanoparticles is a plausible and modifiable environmental risk factor for cardiac oxidative stress and cardiovascular disease, on an international scale.

在全球范围内，暴露于颗粒空气污染是导致心血管疾病死亡率和发病率的主要环境风险因素。迄今为止，急性和慢性心血管影响均归因于肺中颗粒介导的氧化应激和/或通过“次级”途径，包括内皮功能障碍和炎症。但是，越来越多的证据表明，吸入的纳米颗粒通过循环转移到主要器官。识别此类颗粒的组成和细胞内靶标至关重要，因为它们很可能确定其毒性以及对健康的影响。潜在的主要问题是大量工业和交通相关来源排放的富含铁的空气污染纳米颗粒的存在。

在这里，我们首次就地确定了年轻，高暴露人群的心肌线粒体内外源性纳米颗粒（直径约15-40 nm）主要是铁丰富的，并且与其他活性金属（包括铝和镁）共存。钛。这些圆形的电极纳米颗粒（比低污染的对照组多多达约10倍）位于异常的心肌线粒体（例如变形的cr；膜破裂）内。氧化应激标记PrP ^C的测量内质网应激标志物GRP78在高暴露与低污染对照组中发现明显的心室上调。在形状/尺寸/组成方面，线粒体内的颗粒与交通/工业来源排放的富含铁的，燃烧和摩擦衍生的纳米颗粒在路边/城市环境中难以区分。因此，吸入富铁的空气污染纳米颗粒侵入心肌线粒体似乎与线粒体功能障碍以及通过铁催化的Fenton反应过量形成活性氧有关。PrP ^C指示的心室氧化应激和GRP78上调，即使在危险因素最小且无合并症的儿童/年轻人中也很明显。这些新发现表明，在国际范围内，吸入空气中富含金属的纳米颗粒引起的心肌铁超载是对心脏氧化应激和心血管疾病的合理且可改变的环境危险因素。